2022/04/06 更新

写真a

タカキ アキノブ
高木 章乃夫
TAKAKI Akinobu
所属
医歯薬学域 教授(特任)
職名
教授(特任)
外部リンク

学位

  • 医学博士 ( 岡山大学 )

研究キーワード

  • Gastroenterology

  • 消化器内科学

  • Gastroenterology

研究分野

  • ライフサイエンス / 消化器内科学

学歴

  • 岡山大学    

    - 1994年

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    国名: 日本国

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  • 岡山大学   Graduate School, Division of Medical Sciences   Internal Medicine

    - 1994年

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  • 岡山大学   Medical School   Faculty of Medicine

    - 1990年

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    国名: 日本国

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  • 岡山大学   Faculty of Medicine  

    - 1990年

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経歴

  • - Associate Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2012年

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  • - 岡山大学医歯薬学総合研究科 准教授

    2012年

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  • Senior Assistant Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2010年 - 2012年

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  • 岡山大学医歯薬学総合研究科 講師

    2010年 - 2012年

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所属学協会

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委員歴

  • 日本門脈圧亢進症学会   評議員  

    2019年   

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  • 日本肝臓学会   評議員  

    2018年   

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    団体区分:学協会

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  • 厚生労働科学研究費補助金 難治性疾患政策研究事業 「難治性の肝・胆道疾患に関する調査研究」班   研究協力者  

    2016年   

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    団体区分:政府

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  • 日本消化器病学会   学会評議員  

    2012年   

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    団体区分:学協会

    日本消化器病学会

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  • 日本消化器免疫学会   評議員  

    2011年   

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    団体区分:学協会

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  • 日本内科学会   中国支部評議員  

    2009年   

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    団体区分:学協会

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論文

  • A case of focal nodular hyperplasia with hepatic failure treated with liver transplantation.

    Tetsuya Yasunaka, Yasuto Takeuchi, Akinobu Takaki, Fukuo Kondo, Tomoharu Yoshizumi, Kenichi Kohashi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

    Clinical journal of gastroenterology   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure.

    DOI: 10.1007/s12328-021-01529-w

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  • Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma. 国際誌

    Hiroyuki Terasawa, Hideaki Kinugasa, Kazuhiro Nouso, Shumpei Yamamoto, Mami Hirai, Takehiro Tanaka, Akinobu Takaki, Hiroyuki Okada

    World journal of gastroenterology   27 ( 41 )   7134 - 7143   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: It remains unclear which factors, such as tumor volume and tumor invasion, influence circulating tumor DNA (ctDNA), and the origin of ctDNA in liquid biopsy is always problematic. To use liquid biopsies clinically, it will be very important to address these questions. AIM: To assess the origin of ctDNA, clarify the dynamics of ctDNA levels, assess ctDNA levels by using a xenograft mouse after treatment, and to determine whether tumor volume and invasion are related to ctDNA levels. METHODS: Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line. Groups of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA analysis. Analysis of ctDNA was performed by droplet digital PCR, using the human telomerase reverse transcriptase (hTERT) gene. RESULTS: Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8. No hTERT was detected at week 4, but it was detected at week 8. However, in four-site xenograft mice, hTERT was detected both at week 4 and week 6. These experiments revealed that both tumor invasion and tumor volume were associated with the detection of ctDNA. In resection experiments, hTERT was detected at resection, but had decreased by 6 h, and was no longer detected 1 and 3 d after resection. CONCLUSION: We clarified the origin and dynamics of ctDNA, showing that tumor volume is an important factor. We also found that when the tumor was completely resected, ctDNA was absent after one or more days.

    DOI: 10.3748/wjg.v27.i41.7134

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  • Transformation to diffuse large B-cell lymphoma with germinal center B-cell like subtype and discordant light chain expression in a patient with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.

    Hiroki Kobayashi, Noboru Asada, Yuria Egusa, Tomoka Ikeda, Misa Sakamoto, Masaya Abe, Daisuke Ennishi, Masahiro Sakata, Akinobu Takaki, Soichiro Kawahara, Yusuke Meguri, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda

    International journal of hematology   114 ( 3 )   401 - 407   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare indolent B-cell neoplasm, and a gain-of-function mutation in the myeloid differentiation primary response 88 (MYD88), L265P, is a commonly recurring mutation in patients with WM/LPL. Histological transformation of WM/LPL to an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL) is rare, and transformed DLBCL has a worse prognosis than de novo DLBCL, partly because transformed DLBCL is mostly classified as non-germinal center B-cell-like (non-GCB) subtype. We herein describe a 75-year-old man with DLBCL with a history of WM/LPL. DLBCL in this patient showed the GCB subtype, and the light chain restriction of DLBCL was different from that of the antecedent WM/LPL, indicating that the two types of lymphoma cells had distinctive origins. However, DLBCL in this patient harbored the MYD88 L265P mutation, and polymerase chain reaction and Sanger sequencing of the DLBCL and WM/LPL for immunoglobulin heavy chain gene rearrangement suggested a clonal relationship between the two lymphomas. Since the outcome of transformed DLBCL is worse than for de novo DLBCL, it is important to evaluate the clonal relationship between primary WM/LPL and the corresponding transformed DLBCL, even if the DLBCL expresses a GCB subtype or discordant light chain restriction.

    DOI: 10.1007/s12185-021-03157-z

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  • Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma. 国際誌

    Atsushi Oyama, Kazuhiro Nouso, Kenichi Yoshimura, Yuki Morimoto, Shinichiro Nakamura, Hideki Onishi, Akinobu Takaki, Shouta Iwadou, Kazuya Kariyama, Kenji Kuwaki, Kazuhisa Yabushita, Kosaku Sakaguchi, Jyunichi Toshimori, Haruhiko Kobashi, Akio Moriya, Masaharu Ando, Hiroyuki Okada

    Hepatology research : the official journal of the Japan Society of Hepatology   51 ( 6 )   694 - 701   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. METHODS: This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle. RESULTS: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non-HAIC group (n = 35). Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade 2 cholecystitis and grade 2 hyperkalemia. CONCLUSIONS: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.

    DOI: 10.1111/hepr.13633

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  • Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan. 国際誌

    Takuya Adachi, Yasuto Takeuchi, Akinobu Takaki, Atsushi Oyama, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

    International journal of molecular sciences   22 ( 11 )   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tolvaptan is a recently available diuretic that blocks arginine vasopressin receptor 2 in the renal collecting duct. Its diuretic mechanism involves selective water reabsorption by affecting the water reabsorption receptor aquaporin 2. Given that liver cirrhosis patients exhibit hyponatremia due to their pseudo-aldosteronism and usage of natriuretic agents, a sodium maintaining agent, such as tolvaptan, is physiologically preferable. However, large scale studies indicating the patients for whom this would be effective and describing management under its use have been insufficient. The appropriate management of cirrhosis patients treated with tolvaptan should be investigated. In the present review, we collected articles investigating the effectiveness of tolvaptan and factors associated with survival and summarized their management reports. Earlier administration of tolvaptan before increasing the doses of natriuretic agents is recommended because this may preserve effective arterial blood volume.

    DOI: 10.3390/ijms22115582

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  • Abnormal fucosylation of alpha-fetoprotein in patients with nonalcoholic steatohepatitis. 国際誌

    Kazuhiro Nouso, Yoshie Furubayashi, Kazuya Kariyama, Akiko Wakuta, Nozomi Miyake, Kanae Inoue, Yuta Nagai, Shiho Murakami, Takuya Adachi, Atsushi Oyama, Nozomu Wada, Yasuto Takeuchi, Masahiro Sakata, Tetsuya Yasunaka, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Shohei Shiota, Satoshi Yasuda, Hidenori Toyoda, Miwa Kawanaka, Takashi Kumada, Hiroyuki Okada

    Hepatology research : the official journal of the Japan Society of Hepatology   51 ( 5 )   548 - 553   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development. METHODS: Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH). RESULTS: Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort. CONCLUSION: Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.

    DOI: 10.1111/hepr.13626

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  • The transition in the etiologies of hepatocellular carcinoma-complicated liver cirrhosis in a nationwide survey of Japan.

    Hirayuki Enomoto, Yoshiyuki Ueno, Yoichi Hiasa, Hiroki Nishikawa, Shuhei Hige, Yasuhiro Takikawa, Makiko Taniai, Toru Ishikawa, Kohichiroh Yasui, Akinobu Takaki, Koichi Takaguchi, Akio Ido, Masayuki Kurosaki, Tatsuya Kanto, Shuhei Nishiguchi

    Journal of gastroenterology   56 ( 2 )   158 - 167   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC). METHODS: Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases. RESULTS: In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased. CONCLUSIONS: Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.

    DOI: 10.1007/s00535-020-01748-x

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  • High expression of a vascular stricture‐related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long‐term survival after tolvaptan administration for liver cirrhosis

    Takuya Adachi, Akinobu Takaki, Shuichi Sato, Hiroshi Tobita, Haruhiko Kobashi, Masaru Kinomura, Atsuko Nakatsuka, Atsushi Oyama, Nozomu Wada, Masahiro Sakata, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

    Hepatology Research   50 ( 12 )   1347 - 1354   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/hepr.13573

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/hepr.13573

  • Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma. 査読 国際誌

    Daisuke Uchida, Akinobu Takaki, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hiroyuki Okada

    Nutrients   12 ( 6 )   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients' disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.

    DOI: 10.3390/nu12061576

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  • A Phase I/Ib trial of Ad-REIC in liver cancer: study protocol. 査読

    Oyama A, Shiraha H, Uchida D, Iwamuro M, Kato H, Takaki A, Ikeda F, Onishi H, Yasunaka T, Takeuchi Y, Wada N, Iwasaki Y, Sakata M, Okada H, Kumon H

    Future oncology (London, England)   15 ( 31 )   3547 - 3554   2019年11月

  • The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer. 査読

    Matsumoto K, Ohara T, Fujisawa M, Takaki A, Takahara M, Tanaka N, Kato H, Horiguchi S, Yoshida R, Umeda Y, Fushimi S, Yagi T, Matsukawa A, Okada H

    Journal of gastroenterology   54 ( 11 )   1019 - 1028   2019年11月

  • 膵癌におけるFNA検体と切除検体とのPD-L1発現の検討 査読

    松本 和幸, 高木 章乃夫, 大原 利章, 藤澤 真義, 高原 政宏, 加藤 博也, 吉田 龍一, 楳田 祐三, 八木 孝仁, 松川 昭博, 岡田 裕之

    日本消化器病学会雑誌   116 ( 臨増大会 )   A826 - A826   2019年11月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • The Efficacy and Safety of Steroids for Preventing Postembolization Syndrome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma. 査読

    Kuwaki K, Nouso K, Miyashita M, Makino Y, Hagihara H, Moriya A, Adachi T, Wada N, Yasunaka Y, Yasunaka T, Takeuchi Y, Onishi H, Nakamura S, Ikeda F, Shiraha H, Takaki A, Okada H

    Acta medica Okayama   73 ( 4 )   333 - 339   2019年8月

  • Monitoring serum proangiogenic cytokines from hepatocellular carcinoma patients treated with sorafenib. 査読

    Adachi T, Nouso K, Miyahara K, Oyama A, Wada N, Dohi C, Takeuchi Y, Yasunaka T, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Takabatake H, Fujioka SI, Kobashi H, Takuma Y, Iwadou S, Uematsu S, Takaguchi K, Hagihara H, Okada H, Okayama Liver, Cancer Group

    Journal of gastroenterology and hepatology   34 ( 6 )   1081 - 1087   2019年6月

  • THE RELATIONSHIP BETWEEN THE PD-L1 EXPRESSION OF SURGICAL RESECTED AND FINE-NEEDLE ASPIRATION SPECIMENS FOR PATIENTS WITH PANCREATIC CANCER 査読

    Matsumoto Kazuyuki, Ohara Toshiaki, Fujisawa Masayoshi, Takaki Akinobu, Takahara Masahiro, Kato Hironari, Horiguchi Shigeru, Matsukawa Akihiro, Okada Hiroyuki

    GASTROENTEROLOGY   156 ( 6 )   S758   2019年5月

  • Paradoxical Roles of Oxidative Stress Response in the Digestive System before and after Carcinogenesis. 査読

    Takaki A, Kawano S, Uchida D, Takahara M, Hiraoka S, Okada H

    Cancers   11 ( 2 )   2019年2月

  • Predictive Factors for Successful Vaccination Against Hepatitis B Surface Antigen in Patients Who Have Undergone Orthotopic Liver Transplantation. 査読

    Ikeda A, Takaki A, Yasunaka T, Oyama A, Adachi T, Wada N, Onishi H, Ikeda F, Shiraha H, Yoshida K, Kuise T, Nobuoka D, Yoshida R, Umeda Y, Yagi T, Fujiwara T, Okada H

    Acta medica Okayama   73 ( 1 )   41 - 50   2019年2月

  • Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan 査読

    Aiso Mitsuhiko, Takikawa Hajime, Tsuji Keiji, Kagawa Tatehiro, Watanabe Masaaki, Tanaka Atsushi, Sato Ken, Sakisaka Shotaro, Hiasa Yoichi, Takei Yoshiyuki, Ohira Hiromasa, Ayada Minoru, Hashimoto Etsuko, Kaneko Shuichi, Ueno Yoshiyuki, Ohmoto Kenji, Takaki Akinobu, Torimura Takuji, Matsuzaki Yasushi, Tajiri Kazuto, Yoneda Masashi, Ito Takayoshi, Kato Naoya, Ikejima Kenichi, Mochida Satoshi, Yasuda Hiroshi, Sakamoto Naoya

    HEPATOLOGY RESEARCH   49 ( 1 )   105 - 110   2019年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hepr.13288

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  • Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-productive lamina propria CD4+ T cells through AMPK activation 査読

    Takahara M, Takaki A, Hiraoka S, Adachi T, Shimomura Y, Matsushita H, Nguyen T, Koike K, Ikeda A, Takashima S, Yamasaki Y, Inokuchi T, Kinugasa H, Sugihara Y, Harada K, Eikawa S, Morita H, Udono H, Okada H

    Scientific Reports   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-019-48331-w

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  • [Adefovir Dipivoxil-induced Fanconi's Syndrome and Osteomalacia Following Multiple Bone Fractures in a Patient with Chronic Hepatitis B]. 査読

    Makita T, Kanzaki H, Onishi H, Ikeda A, Takaki A, Wada N, Takeuchi Y, Yasunaka T, Ikeda F, Shiraha H, Tanaka Y, Nishihara S, Murakawa K, Kitamura Y, Okada H, Sendo T

    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan   139 ( 4 )   641 - 645   2019年

  • Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. 査読

    Shibata Y, Nakatsuka A, Eguchi J, Miyamoto S, Masuda Y, Awazawa M, Takaki A, Yoshida R, Yagi T, Wada J

    Journal of medical case reports   12 ( 1 )   368   2018年12月

  • Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey.

    Satoru Joshita, Kaname Yoshizawa, Takeji Umemura, Hiromasa Ohira, Atsushi Takahashi, Kenichi Harada, Nguyen Canh Hiep, Koichi Tsuneyama, Masayoshi Kage, Masayuki Nakano, Jong-Hon Kang, Kazuhiko Koike, Mikio Zeniya, Tetsuya Yasunaka, Akinobu Takaki, Takuji Torimura, Masanori Abe, Osamu Yokosuka, Atsushi Tanaka, Hajime Takikawa

    Journal of gastroenterology   53 ( 9 )   1079 - 1088   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Autoimmune hepatitis (AIH) is characterized by progressive inflammation and necrosis of hepatocytes and eventually leads to a variety of phenotypes, including acute liver dysfunction, chronic progressive liver disease, and fulminant hepatic failure. Although the precise mechanisms of AIH are unknown, environmental factors may trigger disease onset in genetically predisposed individuals. Patients with the recently established entity of AIH with acute presentation often display atypical clinical features that mimic those of acute hepatitis forms even though AIH is categorized as a chronic liver disease. The aim of this study was to identify the precise clinical features of AIH with acute presentation. METHODS: Eighty-six AIH patients with acute presentation were retrospectively enrolled from facilities across Japan and analyzed for clinical features, histopathological findings, and disease outcomes. RESULTS: Seventy-five patients were female and 11 were male. Patient age ranged from adolescent to over 80 years old, with a median age of 55 years. Median alanine transaminase (ALT) was 776 U/L and median immunoglobulin G (IgG) was 1671 mg/dL. There were no significant differences between genders in terms of ALT (P = 0.27) or IgG (P = 0.51). The number of patients without and with histopathological fibrosis was 29 and 57, respectively. The patients with fibrosis were significantly older than those without (P = 0.015), but no other differences in clinical or histopathological findings were observed. Moreover, antinuclear antibody (ANA)-positive (defined as × 40, N = 63) and -negative (N = 23) patients showed no significant differences in clinical or histopathological findings or disease outcomes. Twenty-five patients experienced disease relapse and two patients died during the study period. ALP ≥ 500 U/L [odds ratio (OR) 3.20; 95% confidence interval (CI) 1.12-9.10; P < 0.030] and GGT ≥ 200 U/L (OR 2.98; 95% CI 1.01-8.77; P = 0.047) were identified as independent risk factors of disease relapse. CONCLUSIONS: AIH with acute presentation is a newly recognized disease entity for which diagnostic hallmarks, such as ALT, fibrosis, and ANA, are needed. Further investigation is also required on the mechanisms of this disorder. Clinicians should be mindful of disease relapse during patient care.

    DOI: 10.1007/s00535-018-1444-4

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  • Symptoms and health-related quality of life in Japanese patients with primary biliary cholangitis 査読

    Yagi Minami, Tanaka Atsushi, Abe Masanori, Namisaki Tadashi, Yoshiji Hitoshi, Takahashi Atsushi, Ohira Hiromasa, Komori Atsumasa, Yamagiwa Satoshi, Kikuchi Kentaro, Yasunaka Tetsuya, Takaki Akinobu, Ueno Yoshiyuki, Honda Akira, Matsuzaki Yasushi, Takikawa Hajime

    SCIENTIFIC REPORTS   8 ( 1 )   12542   2018年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-31063-8

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  • Beneficial and Paradoxical Roles of Anti-Oxidative Nutritional Support for Non-Alcoholic Fatty Liver Disease. 査読

    Uchida D, Takaki A, Adachi T, Okada H

    Nutrients   10 ( 8 )   2018年7月

  • A subclinical high tricuspid regurgitation pressure gradient independent of the mean pulmonary artery pressure is a risk factor for the survival after living donor liver transplantation. 査読

    Saragai Y, Takaki A, Umeda Y, Matsusaki T, Yasunaka T, Oyama A, Kaku R, Nakamura K, Yoshida R, Nobuoka D, Kuise T, Takagi K, Adachi T, Wada N, Takeuchi Y, Koike K, Ikeda F, Onishi H, Shiraha H, Nakamura S, Morimatsu H, Ito H, Fujiwara T, Yagi T, Okada H

    BMC gastroenterology   18 ( 1 )   62   2018年5月

  • Correction to: Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection.

    Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Kazuaki Chayama

    Journal of gastroenterology   53 ( 5 )   689 - 689   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Unfortunately, in the original publication of this article, the copyright line was incorrectly published in PDF as "© The Author(s) 2017" instead of "©The Author(s) 2017 This article is an open access publication" and also the CC-BY description was not included. The description should be as follows.

    DOI: 10.1007/s00535-017-1409-z

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  • Risk Analysis for Invasive Fungal Infection after Living Donor Liver Transplantation: Which Patient Needs Potent Prophylaxis? 査読

    Utsumi M, Umeda Y, Yagi T, Nagasaka T, Shinoura S, Yoshida R, Nobuoka D, Kuise T, Fuji T, Takagi K, Takaki A, Fujiwara T

    Digestive surgery   2018年4月

  • Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation. 査読

    Ako S, Nakamura S, Nouso K, Dohi C, Wada N, Morimoto Y, Takeuchi Y, Yasunaka T, Kuwaki K, Onishi H, Ikeda F, Shiraha H, Takaki A, Okada H

    Acta medica Okayama   72 ( 1 )   47 - 52   2018年2月

  • 改訂自己免疫性肝炎・原発性胆汁性胆管炎診療ガイドライン 査読

    厚生労働科学研究費補助金, 難治性疾患政策研究事業, 難治性の肝, 胆道疾患に関する調査研究, 班, 自己免疫性肝炎分科会, 原発性胆汁性胆管炎分科会, 田中 篤, 大平 弘正, 高橋 敦史, 小森 敦正, 阿部 雅則, 姜 貞憲, 小池 和彦, 鈴木 義之, 髙木 章乃夫, 有永 照子, 島村 拓司, 中本 伸宏, 原田 憲一, 十河 剛, 乾 あやの, 藤澤 知雄, 吉澤 要, 玄田 拓哉, 銭谷 幹男, 下田 慎治, 竹山 康章, 向坂 彰太郎, 谷合 麻紀子, 橋本 悦子, 中村 稔, 浪崎 正, 吉治 仁志, 本多 彰, 松崎 靖司, 廣原 淳子, 山際 訓, 滝川 一

    肝臓   59 ( 4 )   211 - 216   2018年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation 査読

    Kazuhiro Yoshida, Yuzo Umeda, Akinobu Takaki, Takeshi Nagasaka, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kosei Takagi, Tetsuya Yasunaka, Hiroyuki Okada, Takahito Yagi, Toshiyoshi Fujiwara

    Acta medicinae Okayama   71 ( 5 )   381 - 390   2017年10月

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    掲載種別:研究論文(学術雑誌)  

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  • Association between periodontitis and prognosis of pancreatobiliary tract cancer: A pilot study. 査読

    Maruyama T, Tomofuji T, Machida T, Kato H, Tsutsumi K, Uchida D, Takaki A, Yoneda T, Miyai H, Mizuno H, Ekuni D, Okada H, Morita M

    Molecular and clinical oncology   6 ( 5 )   683 - 687   2017年5月

  • Redox Signaling in NASH 査読

    A. Takaki, D. Uchida, K. Yamamoto

    Liver Pathophysiology: Therapies and Antioxidants   169 - 180   2017年3月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Elsevier  

    The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial and difficult to unify. The progression of benign nonalcoholic fatty liver (NAFL) to progressive nonalcoholic steatohepatitis (NASH) is acknowledged to be a multiple parallel hit process. Oxidative stress is one of the main factors that drives progression of NAFL to NASH, although it is also essential for vital cellular processes. Overaccumulation of long chain fatty acid results in mitochondrial ?-oxidation pathway activation followed by reactive oxygen species (ROS) production. ROS can mediate the oxidative stress response in hepatocytes, Kupffer cells, or hepatic stellate cells resulting in hepatocyte damage, and in proinflammatory and profibrogenic responses that should be well balanced. ROS detoxification pathway signaling is often damaged in NAFLD following ROS accumulation. Inactivation of pro-oxidant production pathways and activation of detoxifying signaling pathways are the required treatment approach.

    DOI: 10.1016/B978-0-12-804274-8.00012-6

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  • The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma. 査読

    Yasuyuki Shimomura, Akinobu Takaki, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Takayuki Maruyama, Naofumi Tamaki, Daisuke Uchida, Hideki Onishi, Kenji Kuwaki, Shinichiro Nakamura, Kazuhiro Nouso, Yasuhiro Miyake, Kazuko Koike, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto, Hiroyuki Okada

    Internal Medicine   Vol.56 ( No.3 )   243 - 251   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44). Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated. Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging. Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

    DOI: 10.2169/internalmedicine.56.7002

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  • Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation 査読

    Kawano Seiji, Takaki Akinobu, Iwamuro Masaya, Yasunaka Tetsuya, Kono Yoshiyasu, Miura Kou, Inokuchi Toshihiro, Kawahara Yoshiro, Umeda Yuzo, Yagi Takahito, Okada Hiroyuki

    BIOMED RESEARCH INTERNATIONAL   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HINDAWI LTD  

    Background and Aims. Gastrointestinal surveillance is a requirement prior to liver transplantation (LT), but small intestine examination is not generally undertaken. The aim of the present studywas to evaluate the safety and efficacy of capsule endoscopy (CE) for patients with end-stage liver disease. Methods. 31 patients who needed LT were enrolled, and 139 patients who underwent CE over the same period of time acted as controls. Results. Frequency of successful achievement of evaluation of the full length of the small bowel, the mean gastric transit time, and the mean small bowel transit time were not significantly different between the two groups. Abnormalities in the small bowel were found in 26 patients. Comparative analysis revealed that history of EV rupture, history of EV treatment, red color sign of EV, and presence of PHG or HCC were significantly associated with patients with &gt;2 two such findings (high score group). Conclusions. Small bowel examination by CE in patients before liver transplantation could be performed safely and is justified by the high rate of abnormal lesions detected particularly in patients with history of EV therapy or bleeding, red color sign, and presence of PHG or HCC. This study was registered in the UMIN Clinical Trial Registry (UMIN 000008672).

    DOI: 10.1155/2017/8193821

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  • Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study. 査読

    Masako Terao, Akinobu Takaki, Takayuki Maruyama, Hiroki Oe, Tetsuya Yasunaka, Naofumi Tamaki, Kazufumi Nakamura, Takaaki Tomofuji, Takahito Yagi, Hiroshi Sadamori, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Kazuhiro Nouso, Daisuke Ekuni, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Manabu Morita, Hiroshi Ito, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    Internal Medicine   Vol.54 ( No.22 )   2815 - 2826   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolar-arterial oxygen gradient (AaDO2) 15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient 25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

    DOI: 10.2169/internalmedicine.54.4889

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  • Hepatic stellate cells promote upregulation of epithelial cell adhesion molecule and epithelial-mesenchymal transition in hepatic cancer cells. 査読

    Nagahara T, Shiraha H, Sawahara H, Uchida D, Takeuchi Y, Iwamuro M, Kataoka J, Horiguchi S, Kuwaki T, Onishi H, Nakamura S, Takaki A, Nouso K, Yamamoto K

    Oncology reports   34 ( 3 )   1169 - 1177   2015年9月

  • Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection 査読

    Shintarou Nanba, Fusao Ikeda, Shin-ichi Fujioka, Yasuyuki Araki, Kouichi Takaguchi, Noriaki Hashimoto, Hiroyuki Seki, Akinobu Takaki, Yoshiaki Iwasaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   69 ( 4 )   237 - 244   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51%), and 89% of them obtained sustained virological response (SVR), while 69% of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence &lt; 80% pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2.

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  • Serum N-glycan profiles in patients with intraductal papillary mucinous neoplasms of the pancreas 査読

    Yutaka Akimoto, Kazuhiro Nouso, Hironari Kato, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Takeshi Tomoda, Naoki Yamamoto, Koichiro Tsutsumi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PANCREATOLOGY   15 ( 4 )   432 - 438   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background/objectives: Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N-glycan profile and to investigate its clinical utility in patients with IPMNs.
    Methods: We measured serum N-glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N-glycan changes and clinical parameters.
    Results: Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve = 0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60-486.4] and the presence of enhancing solid components (OR, 35.8; 95% Cl, 5.39-409.6) were significant risk factors for invasive IPMNs.
    Conclusions: We performed a comprehensive evaluation of the changes in serum N-glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

    DOI: 10.1016/j.pan.2015.05.470

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  • Prognostic Value of Altered N-Glycosylation of Circulating Glycoproteins in Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine 査読

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Hideaki Kinugasa, Hironari Kato, Naoki Yamamoto, Koichiro Tsutsumi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Taku Nakahara, Yoshiaki Miura, Hidehisa Asada, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PANCREAS   44 ( 4 )   551 - 556   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives: The objectives of this study were to examine the whole serum N-glycan profile of patients with unresectable pancreatic cancer and to evaluate the ability of glycans to predict gemcitabine treatment efficacy and patient survival.
    Methods: We collected serum from 52 patients with advanced pancreatic cancer before they began gemcitabine monotherapy. The serum glycan profile was measured through comprehensive quantitative high-throughput glycome analysis and compared with the treatment efficacy and patient survival.
    Results: Of the 61 glycans detected, the serum levels of glycan 4310 (molecular weight [m/z] 1549.566), 6301 (m/z 2032.724), and 9200 (m/z 2010.692) were high in patients with a short time to tumor progression (TTP). Multivariate analysis revealed that a high glycan 9200 concentration was an independent risk factor for shorter TTP (hazard ratio, 2.11; 95% confidence interval, 1.07-4.17) and poor overall survival (hazard ratio, 2.56; 95% confidence interval, 1.08-6.19). The median TTP of patients with up-regulation of 9200 after gemcitabine treatment was shorter than for the remaining patients (91 vs 301 days; P = 0.0005). A similar relationship was observed for overall survival (median, 181 vs 561 days; P = 0.001).
    Conclusions: Glycan 9200 is a possible biomarker predicting gemcitabine efficacy survival in patients with unresectable pancreatic cancer.

    DOI: 10.1097/MPA.0000000000000321

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  • Randomized Trial of Peginterferon Alpha-2b Plus Low and Escalating Dose of Ribavirin in Patients With Chronic Hepatitis C With High Viral Load Genotype 1 査読

    Yoshiaki Iwasaki, Yasuyuki Araki, Hideaki Taniguchi, Ryo-ichi Okamoto, Haruhiko Kobashi, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF MEDICAL VIROLOGY   87 ( 4 )   625 - 633   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    It has been reported that elderly patients with chronic hepatitis C infection cannot tolerate standard combination therapy. In this randomized, controlled trial, the efficacy and safety of peginterferon alpha-2b plus a low and escalating dose of ribavirin in chronic hepatitis C patients with high viral load genotype 1 were investigated. Sixty-two patients were randomized into combination therapy with standard ribavirin dosing (group 1) or low and escalating ribavirin dosing (group 2). Patients were evaluated for safety and efficacy of treatment. There was no significant difference in the prevalence of virological response between the groups throughout the treatment as well as 24 weeks after treatment. However, the response in patients 60 years of age was higher in group 1 than in group 2 at early treatment phase (P=0.015). The prevalence of completion of therapy in patients 60 years of age tended to be higher in group 2 than in group 1 (50% vs. 0%, P=0.055). There was no significant difference in dose modification of peginterferon alpha-2b between the groups. However, dose modification of ribavirin was significantly more frequent in group 1 than in group 2 (60% vs. 24%, P=0.005). These data suggest that combination therapy with low and escalating dosing of ribavirin may be safer in elderly patients than that with standard dosing of ribavirin without impairing the treatment response. J. Med. Virol. 87:625-633, 2015. (c) 2015 Wiley Periodicals, Inc.

    DOI: 10.1002/jmv.24097

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  • Use of non-invasive serum glycan markers to distinguish non-alcoholic steatohepatitis from simple steatosis. 査読

    Yamasaki Y, Nouso K, Miyahara K, Wada N, Dohi C, Morimoto Y, Kinugasa H, Takeuchi Y, Yasunaka T, Kuwaki K, Onishi H, Ikeda F, Miyake Y, Nakamura S, Shiraha H, Takaki A, Iwasaki Y, Amano M, Nishimura S, Yamamoto K

    Journal of gastroenterology and hepatology   30   528 - 534   2015年3月

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    出版者・発行元:3  

    DOI: 10.1111/jgh.12726

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  • Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development 査読

    Yasuto Takeuchi, Fusao Ikeda, Toshiya Osawa, Yasuyuki Araki, Kouichi Takaguchi, Youichi Morimoto, Noriaki Hashimoto, Kousaku Sakaguchi, Tatsuro Sakata, Masaharu Ando, Yasuhiro Makino, Shuji Matsumura, Hiroki Takayama, Hiroyuki Seki, Shintarou Nanba, Yuki Moritou, Tetsuya Yasunaka, Hideki Ohnishi, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    World Journal of Hepatology   7 ( 19 )   2220 - 2228   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Baishideng Publishing Group Co  

    AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5ng/mL before therapy and in non-SVR patients showing AFP ≥ 5ng/mL before and 1year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5ng/mL before therapy and no decrease in AFP to &lt
    5ng/mL 1year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5ng/ mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP &lt
    5ng/mL before therapy than in those showing AFP ≥ 5ng/mL. CONCLUSION: The criteria of AFP &lt
    5ng/mL before and 1year after IFN therapy is a benefical predictor for HCC development in CHC patients.

    DOI: 10.4254/wjh.v7.i19.2220

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  • Local recurrence and complications after percutaneous radiofrequency ablation of hepatocellular carcinoma: a retrospective cohort study focused on tumor location. 査読

    Toshimori J, Nouso K, Nakamura S, Wada N, Morimoto Y, Takeuchi Y, Yasunaka T, Kuwaki K, Ohnishi H, Ikeda F, Shiraha H, Takaki A, Yamamoto K

    Acta medica Okayama   69 ( 4 )   219 - 226   2015年

  • Ultrastructural analysis of a gastric persimmon phytobezoar 査読

    Masaya Iwamuro, Haruo Urata, Masumi Furutani, Yoshinari Kawai, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Kazuhide Yamamoto

    CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY   38 ( 4 )   E85 - E87   2014年9月

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    記述言語:英語   出版者・発行元:ELSEVIER MASSON  

    DOI: 10.1016/j.clinre.2013.11.005

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  • L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway 査読

    Hisashi Ishikawa, Akinobu Takaki, Ryuichiro Tsuzaki, Tetsuya Yasunaka, Kazuko Koike, Yasuyuki Shimomura, Hiroyuki Seki, Hiroshi Matsushita, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    PLOS ONE   9 ( 7 )   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% alpha-tocopherol (alpha-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial beta-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although alpha-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial beta-oxidation and redox system.

    DOI: 10.1371/journal.pone.0100627

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  • Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor 査読

    Yuki Moritou, Fusao Ikeda, Yoshiaki Iwasaki, Nobuynki Baba, Kouichi Takaguchi, Tomonori Senoh, Takuya Nagano, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Ohnishi, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   68 ( 1 )   17 - 22   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p = 0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p = 0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p = 0.049, and &lt;0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy.

    DOI: 10.18926/AMO/52139

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  • In Vitro Analysis of Gastric Phytobezoar Dissolubility by Coca-Cola, Coca-Cola Zero, Cellulase, and Papain 査読

    Masaya Iwamuro, Yoshinari Kawai, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Kazuhide Yamamoto

    JOURNAL OF CLINICAL GASTROENTEROLOGY   48 ( 2 )   190 - 191   2014年2月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1097/MCG.0b013e3182a39116

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  • Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis 査読

    Kazuyuki Matsumoto, Yasuhiro Miyake, Hiroshi Matsushita, Atsuyuki Ohnishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   29 ( 1 )   110 - 115   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and AimRecently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH.
    MethodsSerum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers.
    ResultsPrevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse.
    ConclusionsSerum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.

    DOI: 10.1111/jgh.12340

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  • Predictive impact of polymorphism of PNPLA3 on HCC development after interferon therapy in Japanese patients with chronic hepatitis C. 査読

    Moritou Y, Ikeda F, Iwasaki Y, Baba N, Takaguchi K, Senoh T, Nagano T, Takeuchi Y, Yasunaka T, Ohnishi H, Miyake Y, Takaki A, Nouso K, Yamamoto K

    SpringerPlus   2 ( 1 )   251   2013年12月

  • Erratum: Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma (Journal of Gastroenterology (2012) DOI: 10.1007/s00535-011-0492-9) 査読

    Hideaki Kinugasa, Kazuhiro Nouso, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Shin-Ichiro Nakamura, Hidenori Shiraha, Kenji Kuwaki, Hiroaki Hagihara, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto

    Journal of Gastroenterology   47 ( 4 )   489   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00535-011-0508-5

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  • Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis 査読

    Tetsuya Yasunaka, Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hiroshi Sadamori, Kazuko Koike, Satoshi Hirohata, Masashi Tatsukawa, Daisuke Kawai, Hidenori Shiraha, Yasuhiro Miyake, Fusao Ikeda, Haruhiko Kobashi, Hiroaki Matsuda, Susumu Shinoura, Ryuichi Yoshida, Daisuke Satoh, Masashi Utsumi, Teppei Onishi, Kazuhide Yamamoto

    HEPATOLOGY INTERNATIONAL   5 ( 4 )   918 - 926   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Purpose The combination of hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogues has been accepted as the best treatment to control hepatitis B recurrence after orthotopic liver transplantation (OLT). However, the optimal dose of HBIg remains unclear. We have previously reported that high-dose HBIg in the early period followed by low-dose HBIg with nucleos(t)ide analogues offers reliable and cost-effective control of hepatitis B recurrence. The aim of this study was to investigate intrahepatic hepatitis B virus (HBV) reinfection status with our clinically successful protocol.
    Methods We quantified levels of intrahepatic HBV covalently closed circular (ccc) deoxyribonucleic acid (DNA) and serum hepatitis B core-related antigen (HBcrAg), a new serological marker that can estimate intrahepatic cccDNA levels. Nucleos(t)ide analogues were administered in all cases.
    Results No patients showed recurrence of hepatitis B surface antigen (HBsAg) or HBV-DNA. However, HBV, cccDNA, and HBcrAg were positive in 57% and 48% of patients after OLT, respectively. Pre-OLT serum HBV-DNA and HBcrAg levels correlated linearly with post-OLT cccDNA levels (r = 0.534, P &lt; 0.05, and r = 0.634, P &lt; 0.05, respectively). High serum HBV-DNA and HBcrAg levels, particularly with &gt; 3 log(10) copies/mL and &gt; 4 log(10) IU/mL, respectively, at the time of OLT, were associated with high levels of post-OLT cccDNA. Even with our successful protocol, nearly half of patients showed HBV reinfection.
    Conclusions Patients with high serum HBV-DNA and HBcrAg levels before OLT (particularly &gt; 3 log(10) copies/mL and &gt; 4 log(10) IU/mL, respectively) should be followed with care for HBV recurrence.

    DOI: 10.1007/s12072-011-9265-z

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  • Stage of hepatocellular carcinoma is associated with periodontitis 査読

    Naofumi Tamaki, Akinobu Takaki, Takaaki Tomofuji, Yasumasa Endo, Kenta Kasuyama, Daisuke Ekuni, Tetsuya Yasunaka, Kazuhide Yamamoto, Manabu Morita

    JOURNAL OF CLINICAL PERIODONTOLOGY   38 ( 11 )   1015 - 1020   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim: Periodontitis induces overproduction of reactive oxygen species (ROS). This state increases circulating ROS levels and may affect hepatocellular carcinoma (HCC). The Japan Integrated Stage (JIS) score is a novel staging system for HCC. The objective of the present study was to compare JIS scores in HCC patients with and without periodontitis.
    Material and Methods: We recruited 64 HCC patients comprising 31 chronic periodontitis subjects (HCC + P) and 33 periodontally healthy controls (HCC + H). Their JIS scores were recorded. Serum levels of reactive oxygen metabolites (ROM) from HCC + P, HCC + H and healthy age-and gender-matched subjects with healthy gingiva (control, n = 15) were also assessed for circulating ROS levels.
    Results: The HCC + P and HCC + H groups had similar body mass index, habitual drinking and tobacco exposure data. The HCC + P group showed higher JIS scores than the HCC + H group (p = 0.027). Both the HCC + P and HCC + H groups had higher serum levels of ROM than controls (p &lt; 0.001), while serum levels of ROM in the HCC + P group were a further 25.8% higher than those in the HCC + H group (p &lt; 0.001).
    Conclusion: HCC patients with periodontitis had higher JIS score and circulating ROS level than HCC patients without periodontitis.

    DOI: 10.1111/j.1600-051X.2011.01777.x

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  • Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma 査読

    Koji Miyahara, Kazuhiro Nouso, Takeshi Tomoda, Sayo Kobayashi, Hiroaki Hagihara, Kenji Kuwaki, Junichi Toshimori, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   26 ( 11 )   1604 - 1611   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC.
    Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors.
    Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P = 0.008). The prognosis of all patients with eight high biomarkers was progressive disease.
    Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

    DOI: 10.1111/j.1440-1746.2011.06887.x

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  • Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients 査読

    Masashi Tatsukawa, Akinobu Takaki, Hidenori Shiraha, Kazuko Koike, Yoshiaki Iwasaki, Haruhiko Kobashi, Shin-Ichi Fujioka, Kohsaku Sakaguchi, Kazuhide Yamamoto

    BMC CANCER   11   458   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis. To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.
    Methods: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.
    Results: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.
    Conclusions: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.

    DOI: 10.1186/1471-2407-11-458

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  • Stage of hepatocellular carcinoma is associated with periodontitis. 査読

    Naofumi Tamaki, Akinobu Takaki, Takaaki Tomofuji, Yasumasa Endo, Kenta Kasuyama, Daisuke Ekuni, Tetsuya Yasunaka, Kazuhide Yamamoto, Manabu Morita

    Journal of Clinical Periodontology   Vol.38 ( No.11 )   1015 - 1020   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The HCC + P and HCC + H groups had similar body mass index, habitual drinking and tobacco exposure data. The HCC + P group showed higher JIS scores than the HCC + H group (p = 0.027). Both the HCC + P and HCC + H groups had higher serum levels of ROM than controls (p &lt; 0.001), while serum levels of ROM in the HCC + P group were a further 25.8% higher than those in the HCC + H group (p &lt; 0.001).

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  • Additive improvement induced by bezafibrate in patients with primary biliary cirrhosis showing refractory response to ursodeoxycholic acid 査読

    Yasuto Takeuchi, Fusao Ikeda, Shin-ichi Fujioka, Toshiyuki Takaki, Toshiya Osawa, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto, Tatsuya Itoshima

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   26 ( 9 )   1395 - 1401   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Ursodeoxycholic acid (UDCA) has been widely used in the treatment of patients with primary biliary cirrhosis (PBC). However, some patients are refractory to UDCA. The aim of this study is to clarify the additive improvement induced by bezafibrate in patients refractory to UDCA.
    Methods: This study was a prospective analysis of 37 consecutive PBC patients. All patients were treated first for 6 months with UDCA, and then with bezafibrate, if their alkaline phosphatase (ALP) levels did not decrease more than 40% or within the normal range after 6 months&apos; treatment with UDCA. Clinical parameters were monitored for the subsequent 24 months.
    Result: Twenty-two patients (59%) achieved improvement of ALP levels after the treatment with UDCA. Those patients (Group A) had significantly lower levels of ALP at diagnosis than those with abnormal ALP levels after 6 months&apos; treatment with UDCA (Group B; P = 0.020). They continued UDCA monotherapy, and maintained normal ALP levels at subsequent follow ups. However, immunoglobulin M (IgM) levels remained abnormal in eight patients, whose IgM levels at the time of diagnosis were significantly higher than those whose IgM were normalized after 6 months&apos; treatment with UDCA (P = 0.026). Those in Group B were treated additionally with bezafibrate, and 12 patients (80%) achieved normalALP and IgM levels within 12 months of commencement of therapy.
    Conclusion: Higher ALP level at diagnosis is one of the predictors for UDCA failure. Combination treatment of bezafibrate in addition to UDCA may be an effective treatment for PBC patients refractory to UDCA.

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  • Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein 査読

    Kazuhiro Nouso, Yoshiyuki Kobayashi, Shinichiro Nakamura, Sayo Kobayashi, Hiroki Takayama, Junichi Toshimori, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   26 ( 7 )   1195 - 1200   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Fucosylated alpha-fetoprotein (AFP-L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP-L3 under low AFP (&lt;= 20 ng/mL). The aim of this study was to elucidate the role of AFP-L3 in HCC patients with low AFP conditions.
    Methods: One hundred and ninety six consecutive newly developed HCC patients with low AFP (&lt;= 20 ng/mL) were examined for serum AFP-L3 expression by a newly-developed micro-total analysis system that could stably measure AFP-L3 in low AFP circumstances, and its clinical importance was analyzed.
    Results: Positivity of AFP-L3 in HCC patients was 13.3% at a cut-off level of 10%. Five-year survivals of HCC patients with AFP-L3 (&lt; 10%) and AFP-L3 (&gt;= 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des-gamma carboxy prothrombin were observed in the high AFP-L3 (&gt;= 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR] = 3.24, 95% confidence interval [Cl] = 1.27-8.26), the presence of ascites (RR = 3.44, 95% Cl = 1.22-9.34), multiple tumor number (RR = 3.06, 95% CI = 1.33-7.17), and high AFP-L3 (RR = 8.36, 95% Cl = 2.79-25.5) were risk factors for survival. High AFP-L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048).
    Conclusions: AFP-L3 is a strong prognostic factor for survival even in HCC patients with low AFP (&lt;= 20 ng/mL).

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  • Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine 査読

    Haruhiko Kobashi, Yasuhiro Miyake, Fusao Ikeda, Tetsuya Yasunaka, Ken Nishino, Akio Moriya, Jyunichi Kubota, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Gotaro Yamada, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   41 ( 5 )   405 - 416   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim:
    We conducted this prospective study to elucidate the long-term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis.
    Methods:
    CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6 months in CHB and every 3 months in cirrhosis patients.
    Results:
    A total of 256 subjects with CHB (n = 194) or cirrhosis (n = 62) received ETV (n = 129) or LVD (n = 127) for 4.25 years (range: 0.41-10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and alpha-fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug-resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1%, 17.5%, 43.2%, 46.7% and 53.4%, respectively) than chronic hepatitis (1.6%, 3.5%, 3.5%, 7.1% and 29.6%, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des-gamma-carboxy prothrombin (DCP) was 45.7%/97.3% and 33.3%/96.2%, respectively, with the specificity of AFP being higher than at baseline (64.4%), at the cut-off of 10 ng/mL.
    Conclusion:
    NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10 ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.

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  • Hepatocellular carcinoma occurring in hepatobiliary fibropolycystic disease 査読

    Hideaki Kinugasa, Kazuhiro Nouso, Yoshiyuki Kobayashi, Tetuya Yasunaka, Hideki Onishi, Shin-ichiro Nakamura, Hidenori Shiraha, Hiroki Takayama, Junichi Toshimori, Kenji Kuwaki, Hiroaki Hagihara, Yasuhiro Miyake, Fusao Ikeda, Akinobu Takaki, Haruhiko Kobashi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   41 ( 3 )   277 - 281   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Congenital hepatic fibrosis (CHF) and bile duct hamartomas (von Meyenburg complexes) are hepatobiliary fibropolycystic diseases. There have been several reports of liver neoplasias arising in hepatobiliary fibropolycystic diseases. However, most of them were cholangiocarcinomas and cases involving hepatocellular carcinoma (HCC) are rare. A 51-year-old woman was found to have multiple hepatic tumors by ultrasonography and enhanced computed tomography (CT) during a regular work-up for the recurrence of lung cancer and thyroid cancer, which had been surgically removed 4 and 3 years ago, respectively. Nodules were observed at S3, S5, and S6 (2 cm in diameter). All of the nodules were hyperattenuated at the early arterial phase, and the main tumor at S5 showed hypoattenuation at the delayed phase on dynamic CT and magnetic resonance imaging (MRI). HCC was suspected from these findings. She also suffered from multiple small cystic lesions in the liver. The surgically removed liver showed HCC arising in CHF, which is a rare histological finding.

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  • +49A/G polymorphism of cytotoxic T-lymphocyte antigen 4 gene in type 1 autoimmune hepatitis and primary biliary cirrhosis: A meta-analysis 査読

    Yasuhiro Miyake, Fusao Ikeda, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   41 ( 2 )   151 - 159   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim:
    Recently, the associations of +49A/G polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene with the susceptibility to type 1 autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) have been reported; however these associations are yet to be fully elucidated. This study aimed to identify the associations of CTLA-4 gene +49A/G polymorphisms with the susceptibility to type 1 AIH and PBC by using a meta-analysis.
    Methods:
    PubMed was searched by using the following keywords: "autoimmune hepatitis AND (polymorphism OR polymorphisms)" or "primary biliary cirrhosis AND (polymorphism OR polymorphisms)". Meta-analyses of five studies including 526 patients with type 1 AIH and 631 controls and seven studies including 1500 patients with PBC and 2345 controls were performed.
    Results:
    For type 1 AIH, the odds ratio (OR) of G allele was 1.26 [95% confidence interval (CI) 1.06-1.51] although G/G homozygosity was not associated with the susceptibility to type 1 AIH. On the other hand, the OR of A/A homozygosity for type 1 AIH was 0.66 (95% CI 0.50-0.86). For PBC, the OR of G allele was 1.20 (95% CI 1.06-1.34). Furthermore, G/G homozygosity was significantly associated with the susceptibility to PBC (OR 1.29, 95% CI 1.01-1.66). The OR of A/A homozygosity for PBC was 0.81 (95% CI 0.70-0.94).
    Conclusions:
    This study suggests that CTLA-4 gene +49A/G polymorphisms may be associated with the susceptibility to type 1 AIH and PBC. Especially, while G/G genotype may be associated with the susceptibility to PBC, A/A genotype may be protective against type 1 AIH and PBC.

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  • Prognostic model for hepatocellular carcinoma with time-dependent factors. 査読

    Kuwaki K, Nouso K, Kobayashi Y, Nakamura S, Ito YM, Iwadou S, Hagihara H, Yasunaka T, Toshimori J, Miyatake H, Miyoshi K, Onishi H, Miyake Y, Shoji B, Takaki A, Shiraha H, Iwasaki Y, Kobashi H, Yamamoto K

    Acta medica Okayama   65 ( 1 )   11 - 19   2011年2月

  • Serum levels of platelet-derived growth factor-BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure 査読

    Hiroki Takayama, Yasuhiro Miyake, Kazuhiro Nouso, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Haruhiko Kobashi, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   26 ( 1 )   116 - 121   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Background and Aims:
    In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte-colony stimulating factor (G-CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF).
    Methods:
    Serum levels of nine angiogenic factors (angiopoietin-2, follistatin, G-CSF, hepatocyte growth factor [HGF], interleukin-8, leptin, platelet-derived growth factor [PDGF]-BB, platelet endothelial cell adhesion molecule-1 and VEGF) were measured using the Bio-Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls.
    Results:
    Serum levels of PDGF-BB and VEGF were lower in FHF patients than AH patients and controls (PDGF-BB; 2050 +/- 1572 pg/mL vs 4521 +/- 2419 pg/mL vs 8506 +/- 5500 pg/mL, VEGF; 39 +/- 38 pg/mL vs 144 +/- 122 pg/mL vs 205 +/- 121 pg/mL). By using univariate logistic regression models, serum levels of PDGF-BB and VEGF were associated with poor outcomes. Serum PDGF-BB levels were strongly correlated with serum VEGF levels (r = 0.70). Furthermore, serum PDGF-BB levels were significantly correlated with platelet counts (r = 0.79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38).
    Conclusions:
    We consider that serum levels of PDGF-BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients.

    DOI: 10.1111/j.1440-1746.2010.06441.x

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  • Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis 査読

    Yutaka Nakanishi, Hidenori Shiraha, Shin-ichi Nishina, Shigetomi Tanaka, Minoru Matsubara, Shigeru Horiguchi, Masaya Iwamuro, Nobuyuki Takaoka, Masayuki Uemura, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

    BMC CANCER   11   3   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).
    Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.
    Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.
    Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

    DOI: 10.1186/1471-2407-11-3

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  • Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis. 査読

    Ennishi D, Maeda Y, Niitsu N, Kojima M, Izutsu K, Takizawa J, Kusumoto S, Okamoto M, Yokoyama M, Takamatsu Y, Sunami K, Miyata A, Murayama K, Sakai A, Matsumoto M, Shinagawa K, Takaki A, Matsuo K, Kinoshita T, Tanimoto M

    Blood   116 ( 24 )   5119 - 5125   2010年12月

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  • Laparoscopic findings of reddish markings predict hepatocellular carcinoma in patients with hepatitis B virus-related liver disease. 査読

    Shoji B, Ikeda F, Fujioka S, Kobashi H, Yasunaka T, Miyake Y, Shiraha H, Takaki A, Nouso K, Iwasaki Y, Yamamoto K

    Journal of gastroenterology   45 ( 11 )   1172 - 1182   2010年11月

  • Amino acid substitutions of hepatitis C virus core protein are not associated with intracellular antiviral response to interferon-α in vitro. 査読

    Ikeda F, Dansako H, Nishimura G, Mori K, Kawai Y, Ariumi Y, Miyake Y, Takaki A, Nouso K, Iwasaki Y, Ikeda M, Kato N, Yamamoto K

    Liver international : official journal of the International Association for the Study of the Liver   30 ( 9 )   1324 - 1331   2010年10月

  • Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells 査読

    A. Takaki, M. Tatsukawa, Y. Iwasaki, K. Koike, Y. Noguchi, H. Shiraha, K. Sakaguchi, E. Nakayama, K. Yamamoto

    JOURNAL OF VIRAL HEPATITIS   17 ( 8 )   555 - 562   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.

    DOI: 10.1111/j.1365-2893.2009.01213.x

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  • Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma 査読

    Y. Miyake, A. Takaki, Y. Iwasaki, K. Yamamoto

    JOURNAL OF VIRAL HEPATITIS   17 ( 4 )   287 - 292   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Various clinical studies have indicated that interferon (IFN)-alpha treatment prevents the development of hepatocellular carcinoma (HCC) in people chronically infected with hepatitis C virus. However, it has been controversial whether IFN-alpha treatment prevents HCC recurrence. The aim of this study was to identify the preventive effect of IFN-alpha treatment after curative therapy of primary tumours within the Milan criteria (three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less) on HCC recurrence. We conducted a meta-analysis of five trials including 355 patients (167 patients received IFN-alpha treatment after curative therapy of primary tumours) and estimated relative risks (RRs) and 95% confidence intervals (CIs) for the effect of IFN-alpha on HCC recurrence according to the DerSimonian and Laird method. IFN-alpha treatment after curative therapy of primary tumours significantly prevented HCC recurrence (RR 0.33; 95%CI 0.19-0.58, P &lt; 0.0001) without a significant heterogeneity (Q = 4.52, P = 0.34). An evaluation using the Begg method suggested no evidence of publication bias. Sub-group analyses revealed that IFN-alpha treatment reduced HCC recurrence in two studies achieving sustained virologic response (SVR) rates &gt; 30% (RR 0.20; 95%CI 0.05-0.81, P = 0.02) and in three studies achieving SVR rates &lt; 30% (RR 0.44; 95%CI 0.23-0.84, P = 0.01). In conclusion, IFN-alpha treatment after curative treatment of primary tumour within Milan criteria may be effective for the prevention of HCC recurrence, and higher SVR rate may be associated with better preventive effect of IFN-alpha treatment on HCC recurrence.

    DOI: 10.1111/j.1365-2893.2009.01181.x

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  • Clinical features of autoimmune hepatitis diagnosed based on simplified criteria of the International Autoimmune Hepatitis Group 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Haruhiko Kobashi, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto

    DIGESTIVE AND LIVER DISEASE   42 ( 3 )   210 - 215   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Background: Recently, simplified diagnostic criteria for autoimmune hepatitis have been proposed. Aim: We aimed to evaluate usefulness of the simplified criteria.
    Methods: We applied the simplified criteria to 176 autoimmune hepatitis patients diagnosed according to the revised scoring system proposed in 1999 (original criteria). Furthermore, in order to compare predictabilities between these two diagnostic criteria, we included 168 patients with other liver disease than autoimmune hepatitis.
    Results: Of 176 autoimmune hepatitis patients, 85% were diagnosed with autoimmune hepatitis according to the simplified criteria, and patients diagnosed according to the simplified criteria showed a higher frequency of antinuclear antibodies and/or smooth muscle antibodies of 1:80 or greater and slightly higher serum levels Of immunoglobulin G than those diagnosed according to the original criteria. However, 30% of male patients, 23% of patients with acute presentation, 50% of patients showing histological acute hepatitis and 46% of patients negative for antinuclear antibodies at presentation were not diagnosed with autoimmune hepatitis according to the simplified criteria. The simplified criteria showed lower sensitivity (85% vs. 100%) and higher specificity (99% vs. 93%) for autoimmune hepatitis than the original criteria.
    Conclusions: The simplified criteria may be useless for the diagnosis of patients with atypical features, especially patients with histological acute hepatitis. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.dld.2009.06.013

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  • Evolution of prognostic factors in hepatocellular carcinoma in Japan. 査読

    Nouso K, Kobayashi Y, Nakamura S, Kobayashi S, Toshimori J, Kuwaki K, Hagihara H, Onishi H, Miyake Y, Ikeda F, Shiraha H, Takaki A, Iwasaki Y, Kobashi H, Yamamoto K

    Alimentary pharmacology & therapeutics   31 ( 3 )   407 - 414   2010年2月

  • Autoimmune hepatitis with acute presentation in Japan 査読

    Y. Miyake, Y. Iwasaki, H. Kobashi, T. Yasunaka, F. Ikeda, A. Takaki, K. Yamamoto

    DIGESTIVE AND LIVER DISEASE   42 ( 1 )   51 - 54   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Background: In Caucasians with autoimmune hepatitis, patients with acute presentation have autoimmune thyroiditis and histological zone 3 necrosis more frequently.
    Aim: We aimed at investigating clinical features of Japanese autoimmune hepatitis patients with acute presentation.
    Methods: Of 176 patients retrospectively reviewed, 53 were diagnosed with acute presentation.
    Results: Patients with acute presentation had higher serum levels of bilirubin and transaminase, lower frequencies of autoimmune thyroiditis and antinuclear antibodies of 1:160 or greater, and a higher frequency of zone 3 necrosis. Of the 53 patients with acute presentation, 10 showed histological acute hepatitis; however, advanced staging of fibrosis was found in 13 patients. In patients with acute presentation, those with histological acute hepatitis were younger than those with chronic hepatitis. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels with prednisolone treatment was similar between patients with acute presentation and those with classical presentation.
    Conclusions: In line with previous results, zone 3 necrosis is a histological characteristic of autoimmune hepatitis with acute presentation. Autoimmune hepatitis with acute presentation includes not only histological acute hepatitis but also acute exacerbation of pre-existing chronic disease. On the other hand, Japanese patients with acute presentation may also have different clinical features from Caucasian patients. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.dld.2009.04.009

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  • Acute Hepatitis due to Hepatitis E Virus Genotype 1 As an Imported Infectious Disease in Japan 査読

    Koji Miyahara, Yasuhiro Miyake, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Jong-Hon Kang, Kazuaki Takahashi, Masahiro Arai, Kazuhide Yamamoto

    INTERNAL MEDICINE   49 ( 23 )   2613 - 2616   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    An 18-year-old Nepalese man was admitted due to general malaise and anorexia a month after coming to Japan. Laboratory tests showed elevation of transaminase and positivity for IgM anti-HEV antibody. Serum HEV RNA was detected by RT-PCR amplifications. An HEV genome phylogenetic tree, constructed using an 821-nucleotide sequence in the open reading frame 1, indicated that the genotype was 1. HEV genotype 1 is epidemic in South Asia, Africa and South America, and the incidence of acute hepatitis due to HEV genotype 1 is low in Japan. Thereafter, attention should be paid to HEV genotype 1 infection as an imported infectious disease.

    DOI: 10.2169/internalmedicine.49.4221

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  • Efficacy of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Haruhiko Kobashi, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Ryoichi Okamoto, Kouichi Takaguchi, Hiroshi Ikeda, Yasuhiro Makino, Masaharu Ando, Kohsaku Sakaguchi, Kazuhide Yamamoto

    HEPATOLOGY INTERNATIONAL   3 ( 4 )   556 - 562   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    This study aimed to investigate the efficacy of ursodeoxycholic acid (UDCA) for Japanese patients with autoimmune hepatitis (AIH).
    One hundred forty-seven patients were investigated.
    As initial treatment, 25 patients received UDCA (300-600 mg/day) monotherapy (UDCA group), 40 received a combination of prednisolone (PSL) (a parts per thousand yen20 mg/day) and UDCA (combination group), 68 received PSL monotherapy (PSL group), and 14 received other treatments. During the follow-up, in the UDCA group, PSL was added to 8 of 12 patients failing to achieve the normalization of serum transaminase levels with UDCA monotherapy. Cumulative incidence of the normalization of serum transaminase levels was 64% in the UDCA group, 95% in the combination group, and 94% in the PSL group (log-rank test, P = 0.0001). UDCA group required longest periods until the normalization of serum transaminase levels. Eleven patients, who achieved persistent normalization of serum transaminase levels with UDCA monotherapy, did not reach liver failure or develop hepatocellular carcinoma for 49.7 (range = 13.4-137.3) months. Meanwhile, during the taper of PSL, doses of PSL at the initial relapse were lower in patients treated with PSL and UDCA than in those treated with PSL monotherapy, and initial relapse occurred earlier in patients treated with PSL monotherapy.
    UDCA monotherapy is effective for some Japanese AIH patients; however, UDCA monotherapy for patients with either high-grade inflammatory activity or poor residual capacity of liver function is not recommended because they may reach liver failure before achievement of remission. Meanwhile, additional use of UDCA during the taper of corticosteroids may be effective for the prevention of early relapse.

    DOI: 10.1007/s12072-009-9155-9

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  • HCVコア蛋白質のアミノ酸の違いとIFN応答性との関係についての培養細胞を用いた解析 査読

    池田 房雄, 団迫 浩方, 西村 剛, 河合 良成, 有海 康雄, 池田 正徳, 高木 章乃夫, 岩崎 良章, 加藤 宣之, 山本 和秀

    肝臓   50 ( Suppl.2 )   A515 - A515   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Clinical features of type 1 autoimmune hepatitis in adolescence and early adulthood 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Haruhiko Kobashi, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Ryoichi Okamoto, Kouichi Takaguchi, Hiroshi Ikeda, Yasuhiro Makino, Kohsaku Sakaguchi, Masaharu Ando, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   39 ( 8 )   766 - 771   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Aim:
    The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood.
    Methods:
    Fifteen patients aged &lt; 30 years (group 1) were compared with 79 patients aged between 40 years and 50 years (group 2).
    Results:
    At presentation, patients aged &lt; 30 years accounted for 9% of the study population. Although frequencies of extrahepatic concurrent autoimmune diseases were similar between groups 1 and 2, a tendency toward a lower frequency of concurrent autoimmune thyroiditis was shown in group 1 (0 vs. 18%, P = 0.08). Group 1 had a lower frequency of human leukocyte antigen DR4 (27 vs. 78%, P = 0.002), and histological acute hepatitis was shown more frequently in group 1 (27 vs. 4%, P = 0.002). However, there were no differences in frequencies of the normalization of serum transaminase levels after the introduction of corticosteroid treatment or relapse after the normalization of serum transaminase levels between the two groups.
    Conclusions:
    Japanese type 1 AIH patients in adolescence and early adulthood respond well to corticosteroid treatment. However, they may frequently show atypical features, and the diagnosis of type 1 AIH in adolescence and early adulthood may be difficult and should be made carefully.

    DOI: 10.1111/j.1872-034X.2009.00510.x

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  • Twist expression promotes migration and invasion in hepatocellular carcinoma. 査読

    Matsuo N, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Tanaka S, Nishina S, Nakanishi Y, Uemura M, Takaki A, Nakamura S, Kobayashi Y, Nouso K, Yagi T, Yamamoto K

    BMC cancer   9   240   2009年7月

  • Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Haruhiko Kobashi, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Ryoichi Okamoto, Kouichi Takaguchi, Hiroshi Ikeda, Yasuhiro Makino, Masaharu Ando, Kohsaku Sakaguchi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   39 ( 3 )   241 - 246   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20-30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients.
    A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique.
    Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (&gt;= 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups.
    ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.

    DOI: 10.1111/j.1872-034X.2008.00454.x

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  • Feasibility and Findings of Colonoscopy for Living-donor Liver Transplant Candidates 査読

    Shin Ishikawa, Jun Kato, Motoaki Kuriyama, Koji Takemoto, Toshio Uraoka, Akinobu Takaki, Takahito Yagi, Kohsaku Sakaguchi

    JOURNAL OF CLINICAL GASTROENTEROLOGY   43 ( 1 )   69 - 74   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background and Aims: Living-donor liver transplantation (LDLT) has been widely performed in patients with end-stage liver disease and hepatocellular carcinoma in Japan. Although extrahepatic cancer survey for LDLT candidates is absolutely required. few reports have indicated the optimal surveillance method for colorectal cancer. The aim Of this study is to investigate the feasibility and findings of colonoscopy before LDLT.
    Patients and Methods: Front January 2004 to August 2006. we prospectively, enrolled all of the scheduled LDLT candidates of our hospital for pretransplant colonoscopy examination.
    Results: A total of 81 patients were enrolled For colonoscopy. Of these patients. 67 (83%) could actually undergo colonoscopy. Patients who could bot undergo colonoscopy exhibited more impaired liver Function than those who Could (median Model End-State Liver Disease,core: 25.5 vs. 14.5. P = 0.0003). Among patients who underwent colonoscopy. observation of total colon was attained in 64 (96%). Neoplasia was found in 28 ,,) patients, including 4 patients with adenomas &gt;= 10 mm, 1 patient with adenomas with high-grade dysplasia. and 3 patients with invasive cancer. Patients who had advanced neoplasia (adenoma &gt;= 10 mm. adenomas with high-grade dysplasia. or invasive cancer) were likely to have a lower performance status (PS) (7/8 were PS 3) than those who did not (P = 0.054).
    Conclusions: Clinically, significant tumors were found in a considerable portion Of LDLT candidates. particularly in lower PS patients. Because immunosuppressive agents after transplantation may worsen malignant tumors. colonoscopy before transplantation is recommended in patients who can tolerate the procedure.

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  • Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines. 査読

    Ueda N, Shiraha H, Fujikawa T, Takaoka N, Nakanishi Y, Suzuki M, Matsuo N, Tanaka S, Nishina S, Uemura M, Takaki A, Shiratori Y, Yamamoto K

    Molecular oncology   2 ( 3 )   241 - 249   2008年10月

  • Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis 査読

    Yasuhiro Miyake, Yoshiaki Iwasaki, Akinobu Takaki, Toru Onishi, Ryoichi Okamoto, Kouichi Takaguchi, Hiroshi Ikeda, Yasuhiro Makino, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    HEPATOLOGY RESEARCH   38 ( 1 )   96 - 102   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Aim: Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined.
    Methods: We investigated 79 patients with type 1 autoimmune hepatitis who underwent liver biopsy and were screened for HLA DR status by the polymerase chain reaction sequence specific oligonucleotide hybridization method.
    Results: Fifty-five patients had DR4 and 23 had DR2. Thirteen patients had both DR2 and DR4. None had DR3. Of patients aged &lt; 30 years, 70% did not have DR4. A tendency toward higher serum levels of immunoglobulin G was seen in patients with DR4 compared to those without, while patients with neither DR2 nor DR4 had lower serum levels of immunoglobulin G than those with only DR2 and those with only DR4. Patients with DR2 had a lower frequency of concurrentautoimmune disease. Concurrence of thyroid disease was seen only in patients with DR4. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was not associated with HLA DR status.
    Conclusion: HLA DR status is considered to affect the clinical features of Japanese patients with type 1 autoimmune hepatitis. Japanese patients with DR2 may have different clinical features from others. In addition, diagnoses of type 1 autoimmune hepatitis should be made carefully in Japanese patients with neither DR2 nor DR4 and in those aged &lt; 30 years.

    DOI: 10.1111/j.1872-034X.2007.00204.x

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  • [A case of focal segmental glomerulosclerosis(FSGS) complicated with chronic hepatitis B and treated with steroid and LDL apheresis]. 査読

    Takaki A, Nakatsuka A, Satou C, Iwata Y, Ikeda H, Fukushima M

    Nihon Jinzo Gakkai shi   44 ( 8 )   806 - 812   2002年12月

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  • C型慢性肝炎における自己免疫現象

    坂口孝作, 河本博文, 高木章乃夫

    岡山医学会雑誌   105 ( 7-8 )   795-796   1993年8月

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    掲載種別:研究論文(学術雑誌)  

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  • C型肝炎 自己免疫性肝炎とHCV

    坂口孝作, 河本博文, 高木章乃夫

    臨床消化器内科   7 ( 12 )   2007-2015   1992年11月

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    掲載種別:研究論文(学術雑誌)  

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▼全件表示

書籍等出版物

  • 肝肺症候群(総説)

    高木章乃夫, 安中哲也, 大山淳史, 足立卓哉, 岡田裕之( 担当: 共著 ,  範囲: 筆頭著者)

    日本臨床社  2021年2月 

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  • Liver Pathophysiology

    Elsevier Academic Press  2017年 

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  • Immune mechanisms in non-alcoholic steatohepatitis (NASH).

    iConcept Press  2015年 

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  • 肝疾患Review2006-2007

    日本メディカルセンター東京,東京  2006年 

     詳細を見る

  • 肝疾患Review2006-2007

    日本メディカルセンター東京,東京 

     詳細を見る

MISC

  • 肝疾患の診断と治療 生体肝移植後経過より再考する肝硬変合併肺病変の評価

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 和田 望, 坂田 雅浩, 大西 秀樹, 白羽 英則, 吉田 龍一, 楳田 祐三, 中村 一文, 八木 孝仁, 岡田 裕之

    日本消化器病学会四国支部例会プログラム・抄録集   111回   47 - 47   2019年6月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-四国支部  

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  • 肝細胞癌に対する定位放射線治療の有用性

    大西 秀樹, 高木 章乃夫, 能祖 一裕, 大山 淳史, 足立 卓哉, 和田 望, 坂田 雅浩, 安中 哲也, 池田 房雄, 白羽 英則, 岡田 裕之

    肝臓   60 ( Suppl.1 )   A377 - A377   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌根治的治療後の無再発に寄与する因子としての酸化ストレスの重要性

    室 泰子, 高木 章乃夫, 中村 進一郎, 大山 淳史, 足立 卓哉, 和田 望, 安中 哲也, 大西 秀樹, 白羽 英則, 岡田 裕之

    肝臓   60 ( Suppl.1 )   A533 - A533   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 膵癌におけるFNA検体と切除検体とのPD-L1発現の検討

    松本和幸, 高木章乃夫, 大原利章, 藤澤真義, 高原政宏, 加藤博也, 吉田龍一, 楳田祐三, 八木孝仁, 松川昭博, 岡田裕之

    日本消化器病学会雑誌(Web)   116   2019年

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  • ベルベリンは腸管粘膜CD4+T細胞のAMPKの活性化を介して炎症性サイトカインを制御しマウス慢性腸炎を改善させる

    高原政宏, 高木章乃夫, 平岡佐規子, 安富絵里子, 岡昌平, 平井麻美, 井口俊博, 小池和子, 岡田裕之

    日本臨床免疫学会総会プログラム・抄録集   47th   77   2019年

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    記述言語:日本語  

    J-GLOBAL

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  • 当院でのレゴラフェニブ使用症例の経過と効果症例の特徴

    足立 卓哉, 能祖 一裕, 大山 淳史, 和田 望, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    The Liver Cancer Journal   10 ( Suppl.2 )   43 - 44   2018年12月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • 肝細胞癌に対するシスプラチン肝動注化学療法後に大腸炎を発症した一例

    山本 峻平, 大西 秀樹, 大山 淳史, 足立 卓哉, 和田 望, 坂田 雅浩, 安中 哲也, 池田 房雄, 白羽 英則, 能祖 一裕, 高木 章乃夫, 岡田 裕之

    日本消化器病学会中国支部例会プログラム・抄録集   110回   114 - 114   2018年12月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-中国支部  

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  • DCV+ASV併用療法でSVR24を達成した5ヵ月後に再燃を認めたC型慢性肝炎の一例

    和田 望, 池田 房雄, 大山 淳史, 足立 卓哉, 坂田 雅浩, 安中 哲也, 大西 秀樹, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会中国支部例会プログラム・抄録集   110回   119 - 119   2018年12月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-中国支部  

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  • DAA治療後のSVR後発癌の特徴

    和田 望, 竹内 康人, 池田 房雄, 大山 淳史, 足立 卓哉, 安中 幸, 安中 哲也, 大西 秀樹, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   59 ( Suppl.2 )   A672 - A672   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 抗ドナーHLA抗体陽性の肝移植の短期・長期成績と問題点 抗ドナー抗体陽性生体肝移植の現状と問題点

    楳田 祐三, 八木 孝仁, 田中 健大, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 吉田 一博, 安井 和也, 吉田 真里, 白川 靖博, 柳井 広行, 高木 章乃夫, 藤原 俊義

    移植   53 ( 総会臨時 )   257 - 257   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 進行肝細胞癌におけるソラフェニブ治療の長期生存症例と短期終了症例のそれぞれの特徴

    足立 卓哉, 能祖 一裕, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 高口 浩一, 植松 周二, 高畠 弘行, 萩原 宏明, 岡田 裕之

    The Liver Cancer Journal   ( Suppl.1 )   77 - 77   2018年6月

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    記述言語:日本語   出版者・発行元:(株)メディカルレビュー社  

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  • Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection

    Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David Pugatch, Tami J. Pilot-Matias, Preethi Krishnan, Rajneet K. Oberoi, Wangang Xie, Kazuaki Chayama

    Journal of Gastroenterology   53 ( 4 )   566 - 575   2018年4月

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    記述言語:英語   出版者・発行元:Springer Tokyo  

    Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen
    GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate &lt
     30 mL/min/1.73 m2)
    and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks
    all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA &lt
     15 IU/mL) 12 weeks post-treatment (SVR12). Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis)
    12 GT1/2-infected patients with severe renal impairment (two with cirrhosis)
    and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

    DOI: 10.1007/s00535-017-1396-0

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  • エンテカビル投与後のB型肝硬変患者の長期予後

    坂口 智紘, 竹内 康人, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会雑誌   115 ( 臨増総会 )   A390 - A390   2018年4月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 非アルコール性脂肪性肝疾患における酸化ストレス評価と発癌も見据えた最適な抗酸化療法の探索

    足立 卓哉, 高木 章乃夫, 下村 泰之, 大山 淳史, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 岡田 裕之

    肝臓   59 ( Suppl.1 )   A522 - A522   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝臓 治療 安全かつ確実なRFA治療を目指した超音波技術の工夫 RFAにおける部分的free-hand法の利点と、ファントムを用いた穿刺トレーニング

    中村 進一郎, 竹内 康人, 能祖 一裕, 大西 秀樹, 森井 和彦, 和田 望, 安中 幸, 白羽 英則, 高木 章乃夫, 岡田 裕之

    超音波医学   45 ( Suppl. )   S329 - S329   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

    Hiep Nguyen Canh, Kenichi Harada, Hirofumi Ouchi, Yasunori Sato, Koichi Tsuneyama, Masayoshi Kage, Masayuki Nakano, Kaname Yoshizawa, Atsushi Takahashi, Masanori Abe, Jong-Hon Kang, Kazuhiko Koike, Ayano Inui, Tomoo Fujisawa, Akinobu Takaki, Teruko Arinaga-Hino, Takuji Torimura, Yoshiyuki Suzuki, Keiichi Fujiwara, Mikio Zeniya, Hiromasa Ohira, Atsushi Tanaka, Hajime Takikawa

    JOURNAL OF CLINICAL PATHOLOGY   70 ( 11 )   961 - 969   2017年11月

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    記述言語:英語   出版者・発行元:BMJ PUBLISHING GROUP  

    Aims Although liver biopsy is crucial to diagnose and guide treatment decisions, a detailed histological analysis of autoimmune hepatitis (AIH) with clinically acute presentations has not yet been performed. This study aimed to characterise the histological features and explore potential histological hallmarks to diagnose the acute presentation of AIH.
    Methods We systematically evaluated liver specimens of 87 adult patients with acute presentation of AIH retrospectively enrolled from Japanese multicentre facilities. Each histological feature was predefined by consensus based on the diagnostic criteria.
    Results Key findings were that acute presentation of AIH revealed histological features of both acute hepatitis and chronic hepatitis accompanying various degrees of fibrosis. The prominent features were lobular necrosis/ inflammation (97.7%), plasma cell infiltration (96.4%), emperipolesis (89.3%), pigmented macrophages (84.5%), cobblestone appearance of hepatocytes (82.6%) and perivenular necroinflammatory activity, including centrilobular necrosis (81.4%).
    Conclusions The acute presentation of AIH represents the entire histological spectrum of acute hepatitis and chronic hepatitis with various activity grades and fibrosis stages that clinically correspond to acute-onset AIH and acute exacerbation of classic AIH, respectively. Although there are no pathognomonic features for the pathological diagnosis, the prominent presence of lobular and perivenular necroinflammatory activity, pigmented macrophages and cobblestone appearance of hepatocytes in addition to the classic AIH features, such as plasma cell infiltration and emperipolesis, are useful for the pathological diagnosis of the acute presentation of AIH.

    DOI: 10.1136/jclinpath-2016-204271

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  • 再発肝癌に対する治療戦略 Salvage transplantationの見極め

    楳田 祐三, 八木 孝仁, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 国府島 健, 熊野 健二郎, 高木 弘誠, 吉田 真里, 高木 章乃夫, 藤原 俊義

    移植   52 ( 4-5 )   414 - 415   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 肝生検で診断し得た非典型画像の悪性リンパ腫の1例

    坂口 智紘, 和田 望, 大山 淳史, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   58 ( Suppl.3 )   A827 - A827   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 酸化ストレスマーカーを指標とした肝硬変体液貯留患者のトルバプタン治療

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    肝臓   58 ( Suppl.3 )   A860 - A860   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • HCV関連肝細胞癌の根治後にInterferon-free治療を行った312症例の再発と予後の解析

    中村 進一郎, 能祖 一裕, 岡田 裕之, 大西 秀樹, 白羽 英則, 池田 房雄, 桑木 健志, 安中 哲也, 安中 幸, 竹内 康人, 和田 望, 大山 淳史, 高木 章乃夫, 藤岡 真一, 荒木 康之, 岩堂 昭太, 守本 洋一, 安東 正晴, 守屋 昭男, 萩原 宏明, 金吉 俊彦, 狩山 和也, 谷口 英明, 小橋 春彦, 熊田 卓, 豊田 秀徳, 本村 健太

    肝臓   58 ( Suppl.3 )   A812 - A812   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 移植後C型肝炎に対するインターフェロンフリーDAA治療の高い効果

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 和田 望, 池田 房雄, 楳田 祐三, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 高木 弘誠, 八木 孝仁, 岡田 裕之

    移植   52 ( 4-5 )   416 - 416   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • Living Donor Liver Transplantation for Acute Liver Failure: Comparing Guidelines on the Prediction of Liver Transplantation

    Kazuhiro Yoshida, Yuzo Umeda, Akinobu Takaki, Takeshi Nagasaka, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kosei Takagi, Tetsuya Yasunaka, Hiroyuki Okada, Takahito Yagi, Toshiyoshi Fujiwara

    ACTA MEDICA OKAYAMA   71 ( 5 )   381 - 390   2017年10月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

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  • Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma

    Hiroaki Sawahara, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Ryo Kato, Atsushi Oyama, Teruya Nagahara, Masaya Iwamuro, Shigeru Horiguchi, Koichiro Tsutsumi, Mari Mandai, Tetsushige Mimura, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Masami Watanabe, Masakiyo Sakaguchi, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   32 ( 10 )   1769 - 1777   2017年10月

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    記述言語:英語   出版者・発行元:WILEY  

    Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
    Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
    Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
    Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

    DOI: 10.1111/jgh.13757

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  • DAA治療によるSVR後発癌

    竹内 康人, 池田 房雄, 和田 望, 安中 幸, 安中 哲也, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   58 ( Suppl.2 )   A578 - A578   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝硬変に伴う軽症肺高血圧の病態分類と生体肝移植後生命予後に与える影響

    大山 淳史, 高木 章乃夫, 安中 哲也, 足立 卓哉, 和田 望, 竹内 康人, 大西 秀樹, 中村 進一郎, 白羽 英則, 信岡 大輔, 吉田 龍一, 楳田 祐三, 篠浦 先, 岡田 裕之, 八木 孝仁

    肝臓   58 ( Suppl.2 )   A650 - A650   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 脾摘の功罪からみた生体肝移植における術前脾動脈塞栓術の意義

    楳田 祐三, 八木 孝仁, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 國府島 健, 熊野 健二郎, 高木 弘誠, 伏見 卓郎, 友田 健, 吉田 真里, 加藤 博也, 高木 章乃夫, 藤原 俊義

    移植   52 ( 総会臨時 )   333 - 333   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • トルバプタンによる胸水腹水治療戦略 肝硬変患者の体液貯留に対するトルバプタン効果予測因子としての酸化ストレスマーカーの有用性

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    日本門脈圧亢進症学会雑誌   23 ( 3 )   65 - 65   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • Autoimmune hepatitis in Japan: trends in a nationwide survey

    Atsushi Takahashi, Teruko Arinaga-Hino, Hiromasa Ohira, Takuji Torimura, Mikio Zeniya, Masanori Abe, Kaname Yoshizawa, Akinobu Takaki, Yoshiyuki Suzuki, Jong-Hon Kang, Nobuhiro Nakamoto, Tomoo Fujisawa, Koji Yonemoto, Atsushi Tanaka, Hajime Takikawa

    JOURNAL OF GASTROENTEROLOGY   52 ( 5 )   631 - 640   2017年5月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    A nationwide survey of autoimmune hepatitis (AIH) patients was performed in Japan in 2015. The aims of this study were to elucidate the trends and characteristics of AIH in Japan, in addition to identifying differences in AIH between acute hepatitis and chronic hepatitis.
    Questionnaires about patients with AIH diagnosed from 2009 to 2013 were sent to 437 hospitals or clinics with hepatology specialists.
    A total of 1682 patients were enrolled. The mean age at diagnosis was 60.0 years, and 87.1 % of patients were female. Serum immunoglobulin G levels were high, peaking at 1.5-2.0 g/dL. Histological diagnoses of chronic hepatitis, acute hepatitis, and cirrhosis were seen in 79.6, 11.7, and 6.7 % of patients respectively. In addition to elevation of aminotransferase levels, the frequencies of emperipolesis and human leukocyte antigen (HLA)-DR2 positivity were higher in patients with acute hepatitis than in those with chronic hepatitis. Approximately 80 % of patients were treated with corticosteroids, and in 97.7 % of them, their condition improved. Steroid pulse therapy was more frequently given to patients with acute hepatitis than to those with chronic hepatitis.
    In the present nationwide survey of AIH patients in Japan, patients with acute hepatitis had clinical features different from those of patients with chronic hepatitis.

    DOI: 10.1007/s00535-016-1267-0

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  • Prospective evaluation of the factors predicting the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.

    Takuya Adachi, Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Koichi Takaguchi, Shuji Uematsu, Shouta Iwadou, Yoshitaka Takuma, Hiroaki Hagihara, Hiroyuki Takabatake, Akinobu Takaki, Hiroyuki Okada

    JOURNAL OF CLINICAL ONCOLOGY   35   2017年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2017.35.15_suppl.e15674

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  • Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm

    Shigeru Horiguchi, Hironari Kato, Hidenori Shiraha, Koichiro Tsutsumi, Naoki Yamamoto, Kazuyuki Matsumoto, Takeshi Tomoda, Daisuke Uchida, Yutaka Akimoto, Syou Mizukawa, Takehiro Tanaka, Koichi Ichimura, Akinobu Takaki, Takahito Yagi, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   32 ( 4 )   925 - 931   2017年4月

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    記述言語:英語   出版者・発行元:WILEY  

    Background and Aim Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN.
    Methods In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD.
    Results By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r=0.83, P&lt;0.0001) and pathological grade (P=0.0074).
    Conclusions Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

    DOI: 10.1111/jgh.13594

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  • 肝腫瘤に対する穿刺・治療の進歩 穿刺用マイクロコンベックスプローブに求められるもの

    中村 進一郎, 大西 秀樹, 桑木 健志, 竹内 康人, 白羽 英則, 和田 望, 安中 幸, 能祖 一裕, 高木 章乃夫, 岡田 裕之

    超音波医学   44 ( Suppl. )   S260 - S260   2017年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • PREDICTION OF PROGNOSIS: RETREATMENT WITH TACE ON DEMAND IN PATIENTS WITH HCC

    Nozomu Wada, Kazuhiro Nouso, Shouta Iwado, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    GASTROENTEROLOGY   152 ( 5 )   S1174 - S1174   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝硬変体液貯留に対するトルバプタンの効果予測因子としての酸化ストレスの重要性

    足立 卓哉, 高木 章乃夫, 佐藤 秀一, 大山 淳史, 下村 泰之, 和田 望, 竹内 康人, 安中 幸, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 岡田 裕之

    肝臓   58 ( Suppl.1 )   A407 - A407   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • SUBCLINICAL PULMONARY HYPERTENSION IS A STRONG RISK OF POST LIVING DONOR LIVER TRANSPLANTATION SURVIVAL FOR LIVER CIRRHOSIS

    Yosuke Saragai, Akinobu Takaki, Yuzo Umeda, Tetsuya Yasunaka, Ryuji Kaku, Kazufumi Nakamura, Takahito Yagi, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Takuya Adachi, Yasuyuki Shimomura, Nozomu Wada, Kenji Kuwaki, Fusao Ikeda, Hideki Onishi, Hidenori Shiraha, Shinichiro Nakamura, Hiroshi Ito, Toshiyoshi Fujiwara, Hiroyuki Okada

    GASTROENTEROLOGY   152 ( 5 )   S1122 - S1122   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma

    Kazuhiro Nouso, Kazuya Kariyama, Shinichiro Nakamura, Ayano Oonishi, Akiko Wakuta, Atsushi Oyama, Soichiro Ako, Chihiro Dohi, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   32 ( 3 )   695 - 700   2017年3月

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    記述言語:英語   出版者・発行元:WILEY  

    Background and Aim: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC.
    Methods: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching.
    Results: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (&gt; 30 mm, hazard ratio = 1.685, P = 0.043), high des-gamma-carboxyprothrombin (&gt; 100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group.
    Conclusions: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

    DOI: 10.1111/jgh.13586

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  • Early Chimerism After Liver Transplantation Reflects the Clinical Course of Recurrent Hepatitis C

    Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C. Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi

    ANNALS OF TRANSPLANTATION   22   156 - 165   2017年3月

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    記述言語:英語   出版者・発行元:INT SCIENTIFIC LITERATURE, INC  

    Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C.
    Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined.
    Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism.
    Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

    DOI: 10.12659/AOT.900494

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  • Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma (vol 35, pg 2576, 2016)

    Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

    ONCOLOGY REPORTS   37 ( 3 )   1921 - 1921   2017年3月

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    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    DOI: 10.3892/or.2017.5419

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  • Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease

    Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

    HEPATOLOGY INTERNATIONAL   11 ( 1 )   115 - 124   2017年1月

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    記述言語:英語   出版者・発行元:SPRINGER  

    The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH.
    A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified.
    One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-gamma-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation.
    IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

    DOI: 10.1007/s12072-016-9773-y

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  • Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs

    Yoshiyasu Kono, Seiji Kawano, Akinobu Takaki, Yasuyuki Shimomura, Masahiro Onji, Hisashi Ishikawa, Sakuma Takahashi, Joichiro Horii, Sayo Kobayashi, Daisuke Kawai, Kazuhide Yamamoto, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   32 ( 1 )   136 - 145   2017年1月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and AimVideo-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model.
    MethodsA total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group).
    ResultsSerum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P&lt;0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P&lt;0.01). Serum d-ROM levels were lower in NC and NE than N (P&lt;0.01), and OXY levels were higher in NC than N and NE (P&lt;0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N.
    ConclusionsNon-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

    DOI: 10.1111/jgh.13424

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  • A sofosbuvir-based direct-acting antiviral treatment regimen exhibits a strong protective effect against post-liver transplantation chronic hepatitis C recurrence

    Atsushi Oyama, Akinobu Takaki, Tetsuya Yasunaka, Takuya Adachi, Fusao Ikeda, Nozomu Wada, Yasuhito Takeuchi, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Kosei Takagi, Takashi Kuise, Daisuke Nobuoka, Ryuichi Yoshida, Yuzo Umeda, Mari Yoshida, Chisato Arimori, Takahito Yagi, Hiroyuki Okada

    Acta Hepatologica Japonica   58 ( 11 )   599 - 604   2017年

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    記述言語:日本語   出版者・発行元:Japan Society of Hepatology  

    The efficacy and safety of anti-hepatitis C virus (HCV. direct-acting antivirals were evaluated in postorthotopic liver transplantation patients. There were 29 patients with HCV genotype 1 and 2 with genotype 2. Of the 29 genotype 1 patients, 5 received daclatasvir (DCV. + asunaprevir (ASV), and 25 received sofosbuvir (SOF. + ledipasvir (LDV), including 1 who had failed DCV + ASV. Both genotype 2 patients received SOF + ribavirin. Four patients with DCV + ASV completed the protocol, and 3 of them achieved a sustained viral re-sponse for 24 weeks (SVR24). All of the patients who received SOF + LDV and SOF + RBV achieved SVR24 with minor adverse events. In post-liver transplantation patients, SOF-based regimens showed highly satisfactory efficacy and safety.

    DOI: 10.2957/kanzo.58.599

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  • Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation (vol 2017, 8193821, 2017)

    Seiji Kawano, Akinobu Takaki, Masaya Iwamuro, Tetsuya Yasunaka, Yoshiyasu Kono, Kou Miura, Toshihiro Inokuchi, Yoshiro Kawahara, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

    BIOMED RESEARCH INTERNATIONAL   2017   406 - 410   2017年

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    記述言語:英語   出版者・発行元:HINDAWI LTD  

    DOI: 10.1155/2017/6418529

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  • The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma

    Yasuyuki Shimomura, Akinobu Takaki, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Takayuki Maruyama, Naofumi Tamaki, Daisuke Uchida, Hideki Onishi, Kenji Kuwaki, Shinichiro Nakamura, Kazuhiro Nouso, Yasuhiro Miyake, Kazuko Koike, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto, Hiroyuki Okada

    INTERNAL MEDICINE   56 ( 2 )   243 - 251   2017年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC).
    Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44).
    Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated.
    Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging.
    Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

    DOI: 10.2169/internalmedicine.56.7002

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  • Sufficient management of alert system of positive test results for HBV and HCV infection in electronic medical chart for facilitating hepatological consultation

    Yasuyuki Shimomura, Yousuke Fujii, Fusao Ikeda, Tetsuya Yasunaka, Noriko Yamasaki, Ikuko Kasahara, Naomi Inuyama, Michihiro Koyama, Shihoko Namba, Yasuto Takeuchi, Nozomu Wada, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Acta Hepatologica Japonica   58 ( 8 )   427 - 434   2017年

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    記述言語:日本語   出版者・発行元:Japan Society of Hepatology  

    Alert for positive results of hepatitis tests in electronic medical chart is helpful for management of hepatitis carriers at non-hepatology departments. Further attempts for sufficient hepatological consultations in this alert system, such as explaining the test results to the subjects by mailing notification forms with referral to the hepatologists were adopted. The notification forms were re-mailed to the subjects without the reply in 6 months. Aggregate analysis by reviewing the charts of the subjects confirmed that the rate of hepatological consultation was improved from 49% to 72% with further attempts (p&lt
    0.001, the chi-square test). Mailing notification forms with referral to the hepatologists can be helpful for facilitating hepatological consultation in alert system of positive test results for HBV and HCV infection in electronic medical chart.

    DOI: 10.2957/kanzo.58.427

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  • Hepatic and Gastric Involvement in a Case of Systemic Sarcoidosis Presenting with Rupture of Esophageal Varices

    Hiroaki Saito, Masayasu Ohmori, Masaya Iwamuro, Takehiro Tanaka, Nozomu Wada, Tetsuya Yasunaka, Akinobu Takaki, Hiroyuki Okada

    INTERNAL MEDICINE   56 ( 19 )   2583 - 2588   2017年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    A 46-year-old woman presented with massive hematemesis, caused by the rupture of esophageal varices. The laboratory investigations showed pancytopenia, and imaging tests revealed hepatosplenomegaly and ascites. A diagnosis of systemic sarcoidosis was made based on biopsies of the liver, stomach, lungs, heart, and skin. Although fat deposition was predominant, non-caseating granuloma and cirrhotic changes were found in the liver. Non-caseating granuloma was also identified in a biopsy specimen from minute depressions of the gastric folds. This case illustrates the rare involvement of the digestive system in a case of systemic sarcoidosis.

    DOI: 10.2169/internalmedicine.8768-16

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  • Correction to

    Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs,Rebecca Redman, David Pugatch, Tami J. Pilot-Matias, Preethi Krishnan, Rajneet, K. Oberoi, Wangang Xie, Kazuaki Chayama

    Journal of Gastroenterology, Gastroenterologia Japonica   873 - 882   2017年

  • Usefulness of the seminars on liver disease at workplace to improve work environment associated with viral hepatitis

    Shihoko Namba, Fusao Ikeda, Yasuyuki Shimomura, Naomi Inuyama, Shinnosuke Okubo, Takashi Makita, Yuko Hasegawa, Kenji Iwai, Akiko Hosoba, Rumi Miura, Yosuke Fujii, Tetsuya Yasunaka, Yasuto Takeuchi, Nozomu Wada, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Acta Hepatologica Japonica, Kanzo   58 ( 5 )   304 - 306   2017年

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  • Low-dose FP療法が奏効した切除不能混合型肝癌の1例

    加藤 小百合, 竹内 康人, 和田 望, 森元 裕貴, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    日本消化器病学会雑誌   113 ( 12 )   2050 - 2056   2016年12月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

    症例は50歳代、女性。肝左葉を占める、肝内多発転移・門脈腫瘍塞栓をともなう混合型肝癌と診断された。肝細胞癌成分が有意と判断し、肝細胞癌に準じた化学療法を導入した。Sorafenib・CDDP肝動注療法では病勢と全身状態の悪化を認めたが、Low-dose FP(LFP)療法は奏効を認め、長期生存が得られている。今回LFP療法が、切除不能な混合型肝癌の治療の選択肢としても有効である可能性が示唆された。(著者抄録)

    DOI: 10.11405/nisshoshi.113.2050

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  • 肝移植1年後生存に関与する潜在的門脈肺高血圧症の重要性

    高木 章乃夫, 安中 哲也, 麻植 浩樹, 中村 進一郎, 大西 秀樹, 桑木 健志, 中村 一文, 楳田 祐三, 八木 孝仁, 岡田 裕之

    超音波医学   43 ( 6 )   776 - 777   2016年11月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • 非小細胞肺癌切除症例における術前血漿中抗RPL29抗体価と予後

    山本 寛斉, 高木 章乃夫, 林 達朗, 古川 公之, 田尾 裕之, 枝園 和彦, 宗 淳一, 大谷 真二, 三好 健太郎, 杉本 誠一郎, 山根 正修, 大藤 剛宏, 岡部 和倫, 三好 新一郎, 豊岡 伸一

    肺癌   56 ( 6 )   518 - 518   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • miR-1246 and miR-4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer

    Tatsuya Machida, Takaaki Tomofuji, Takayuki Maruyama, Toshiki Yoneda, Daisuke Ekuni, Tetsuji Azuma, Hisataka Miyai, Hirofumi Mizuno, Hironari Kato, Koichiro Tsutsumi, Daisuke Uchida, Akinobu Takaki, Hiroyuki Okada, Manabu Morita

    ONCOLOGY REPORTS   36 ( 4 )   2375 - 2381   2016年10月

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    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR-1246, miR-3976, miR-4306, and miR-4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR-1246, miR-3976, miR-4306, and miR-4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real-time PCR (RT-qPCR), the relative expression ratios of miR-1246 and miR-4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR-1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR-4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR-1246 and miR-4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR-1246 and miR-4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

    DOI: 10.3892/or.2016.5021

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  • 肝 C型肝炎についてup to date 肝移植後のC型肝炎ウイルス治療の進歩 ソホスブビル含有治療の有用性

    高木 章乃夫, 安中 哲也, 足立 卓哉, 池田 房雄, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 高木 弘誠, 八木 孝仁, 岡田 裕之

    移植   51 ( 総会臨時 )   223 - 223   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 乏血性腫瘤におけるEOB-MRIを用いた肝癌の診断手順

    土肥 千紘, 能祖 一裕, 赤穂 宗一郎, 和田 望, 森元 裕貴, 竹内 康人, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   57 ( Suppl.2 )   A610 - A610   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝移植後の腎機能保持を狙った降圧戦略

    高木 章乃夫, 安中 哲也, 八木 孝仁, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 岡田 裕之

    移植   51 ( 総会臨時 )   237 - 237   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 肝動注化学療法から分子標的薬への切り替えのタイミング 肝機能と早期治療効果判定の観点から

    大西 秀樹, 能祖 一裕, 中村 進一郎, 和田 望, 安中 幸, 竹内 康人, 安中 哲也, 桑木 健志, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   57 ( Suppl.2 )   A562 - A562   2016年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer

    H. Sawahara, H. Shiraha, D. Uchida, H. Kato, T. Nagahara, M. Iwamuro, J. Kataoka, S. Horiguchi, M. Watanabe, M. Sakaguchi, A. Takaki, K. Nouso, Y. Nasu, H. Kumon, H. Okada

    CANCER GENE THERAPY   23 ( 8 )   278 - 283   2016年8月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pantreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied, Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

    DOI: 10.1038/cgt.2016.31

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  • Potential of alpha-fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma

    Chihiro Dohi, Kazuhiro Nouso, Koji Miyahara, Yuki Morimoto, Nozomu Wada, Hideaki Kinugasa, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    HEPATOLOGY RESEARCH   46 ( 9 )   916 - 923   2016年8月

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    記述言語:英語   出版者・発行元:WILEY  

    AimRecurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by -fetoprotein (AFP).
    MethodsWe enrolled 357 consecutive patients who underwent complete ablation by RFA for primary HCC (3cm, 3 tumors) and analyzed the correlation between 17 critical parameters, including AFP and HCC recurrence.
    ResultsRecurrence was observed in 236 patients during a mean observation period of 54.3months. Multivariate analysis revealed that multiple tumors (risk ratio [RR]=1.70, 95% confidence interval [CI]=1.27-2.26, P&lt;0.001), high AFP (&gt;10ng/mL, RR=1.45, 95% CI=1.09-1.94, P&lt;0.001) and high des--carboxyprothrombin (&gt;40 mAU/mL, RR=1.52, 95% CI=1.13-2.02, P&lt;0.005) were significantly correlated with recurrence. AFP was selected as a significant factor even when the cut-off level was set lower (5ng/mL). The risk of recurrence increased linearly according to the increase of the lowest AFP level after RFA and the adjusted ratios relative to AFP less than 5ng/mL were 1.56, 2.14, 2.57 and 3.13 in AFP 5-10ng/mL, 10-20ng/mL, 20-50ng/mL and over 50ng/mL, respectively. In addition, the recurrence rate was predicted by the AFP level after RFA, regardless of the level before the treatment.
    ConclusionAFP less than 5ng/mL after curative RFA was an important predictor of a better prognosis and was considered to indicate the low carcinogenic potential of the non-cancerous liver.

    DOI: 10.1111/hepr.12636

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  • 肝移植と門脈圧亢進症 肝移植1年後生存に関与する術前リスクとしての潜在的門脈肺高血圧症の重要性

    皿谷 洋祐, 高木 章乃夫, 足立 卓哉, 安中 哲也, 麻植 浩樹, 中村 一文, 楳田 祐三, 八木 孝仁, 岡田 裕之

    日本門脈圧亢進症学会雑誌   22 ( 3 )   101 - 101   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 【「移植臓器における原疾患の再発」】 移植臓器におけるC型肝炎の再発

    高木 章乃夫, 安中 哲也, 信岡 大輔, 吉田 龍一, 楳田 祐三, 篠浦 先, 八木 孝仁

    移植   51 ( 2-3 )   92 - 99   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

    DOI: 10.11386/jst.51.2-3_092

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  • 肝移植と門脈圧亢進症 肝移植予定患者における門脈圧亢進症性小腸炎の検討 前向きコホート研究の結果から

    川野 誠司, 高木 章乃夫, 安中 哲也, 楳田 祐三, 八木 孝仁, 岡田 裕之

    日本門脈圧亢進症学会雑誌   22 ( 3 )   101 - 101   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Hiroaki Sawahara, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   31 ( 6 )   1154 - 1159   2016年6月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
    MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
    ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
    ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

    DOI: 10.1111/jgh.13259

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  • Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

    Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

    ONCOLOGY REPORTS   35 ( 5 )   2576 - 2582   2016年5月

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    記述言語:英語   出版者・発行元:SPANDIDOS PUBL LTD  

    Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

    DOI: 10.3892/or.2016.4681

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  • Oxidative Stress Controlling Agents Are Effective for NSAIDs-Induced Small Intestinal Injuries

    Yoshiyasu Kono, Akinobu Takaki, Seiji Kawano, Hiroyuki Okada

    GASTROENTEROLOGY   150 ( 4 )   S693 - S693   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Characteristics of HCC Patients With hTERT Promoter Mutation

    Soichiro Ako, Kazuhiro Nouso, Hideaki Kinugasa, Takuya Adachi, Chihiro Dohi, Yuuki Morimoto, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Shinichi Fujioka, Hiroyuki Okada

    GASTROENTEROLOGY   150 ( 4 )   S1152 - S1152   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • The Pattern of Recurrence Associated With the Prognosis of the Patients With Hepatocellular Carcinoma After Radiofrequency Ablation

    Shinichiro Nakamura, Kazuhiro Nouso, Hideki Onishi, Kenji Kuwaki, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Tetsuya Yasunaka, Yuki Yasunaka, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto, Hiroyuki Okada

    GASTROENTEROLOGY   150 ( 4 )   S1135 - S1135   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Serum IP-10 Is a Highly Sensitive Marker for Discriminating Non-Alcoholic Fatty Liver and Non-Alcoholic Steatohepatitis

    Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuko Koike, Kazuhiro Nouso, Hiroyuki Okada

    GASTROENTEROLOGY   150 ( 4 )   S1091 - S1091   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • データマイニング手法を用いた非侵襲的肝線維化診断法によるC型肝硬変症例の抽出

    桑木 健志, 中村 進一郎, 安中 幸, 竹内 康人, 安中 哲也, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    超音波医学   43 ( Suppl. )   S673 - S673   2016年4月

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    記述言語:日本語   出版者・発行元:(公社)日本超音波医学会  

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  • Changes of Immunoglobulin-Bound Glycans in Patients With Gastro-Intestinal Cancers

    Chihiro Dohi, Kazuhiro Nouso, Soichiro Ako, Yuuki Morimoto, Koji Miyahara, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    GASTROENTEROLOGY   150 ( 4 )   S614 - S614   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C

    Shintaro Nanba, Fusao Ikeda, Nobuyuki Baba, Koichi Takaguchi, Tomonori Senoh, Takuya Nagano, Hiroyuki Seki, Yasuto Takeuchi, Yuki Moritou, Tetsuya Yasunaka, Hideki Ohnishi, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    JOURNAL OF CLINICAL PATHOLOGY   69 ( 3 )   226 - 233   2016年3月

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    記述言語:英語   出版者・発行元:BMJ PUBLISHING GROUP  

    Background Oxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC) after interferon therapy has not been established.
    Methods We investigated the impact of oxidative stress and iron deposition on HCC development after therapy with pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and intracellular iron homeostasis was evaluated in liver tissues, peripheral blood mononuclear cells and sera.
    Results Of 203 patients enrolled, 13 developed HCC during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were significantly associated with HCC development in multivariate analysis (p=0.0012) which was also significantly correlated with severity of hepatic iron deposition before therapy (p&lt;0.0001). Systemic and intracellular iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5) expression levels were significantly suppressed in CHC patients (p=0.0032 and p=0.016, respectively) despite their significantly higher levels of serum iron and ferritin compared with controls. However, intracellular iron regulators of FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron deposition. Significant correlations were observed among IL-6, bone morphogenetic protein 6, hepcidin and ferroportin, as regards systemic iron regulation.
    Conclusions Measurement of hepatic oxidative stress before antiviral therapy is useful for the prediction of HCC development after interferon therapy. Low baseline levels of the intracellular iron regulators of FBXL5 in addition to a suppressed hepcidin level might be associated with severe hepatic iron deposition in CHC patients.

    DOI: 10.1136/jclinpath-2015-203215

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  • Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C

    Shintaro Nanba, Fusao Ikeda, Nobuyuki Baba, Koichi Takaguchi, Tomonori Senoh, Takuya Nagano, Hiroyuki Seki, Yasuto Takeuchi, Yuki Moritou, Tetsuya Yasunaka, Hideki Ohnishi, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    JOURNAL OF CLINICAL PATHOLOGY   69 ( 3 )   226 - 233   2016年3月

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    記述言語:英語   出版者・発行元:BMJ PUBLISHING GROUP  

    Background Oxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC) after interferon therapy has not been established.
    Methods We investigated the impact of oxidative stress and iron deposition on HCC development after therapy with pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and intracellular iron homeostasis was evaluated in liver tissues, peripheral blood mononuclear cells and sera.
    Results Of 203 patients enrolled, 13 developed HCC during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were significantly associated with HCC development in multivariate analysis (p=0.0012) which was also significantly correlated with severity of hepatic iron deposition before therapy (p&lt;0.0001). Systemic and intracellular iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5) expression levels were significantly suppressed in CHC patients (p=0.0032 and p=0.016, respectively) despite their significantly higher levels of serum iron and ferritin compared with controls. However, intracellular iron regulators of FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron deposition. Significant correlations were observed among IL-6, bone morphogenetic protein 6, hepcidin and ferroportin, as regards systemic iron regulation.
    Conclusions Measurement of hepatic oxidative stress before antiviral therapy is useful for the prediction of HCC development after interferon therapy. Low baseline levels of the intracellular iron regulators of FBXL5 in addition to a suppressed hepcidin level might be associated with severe hepatic iron deposition in CHC patients.

    DOI: 10.1136/jclinpath-2015-203215

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  • Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis

    Atsuko Nakatsuka, Makoto Matsuyama, Satoshi Yamaguchi, Akihiro Katayama, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Daisuke Ogawa, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Eijiro Watanabe, Jun Wada

    SCIENTIFIC REPORTS   6   2016年2月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt-/-mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt-/-mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4 alpha resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities.

    DOI: 10.1038/srep21721

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  • Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients

    Tetsuya Yasunaka, Fusao Ikeda, Nozomu Wada, Yuki Morimoto, Shin-ichi Fujioka, Junichi Toshimori, Haruhiko Kobashi, Kazuya Kariyama, Yoichi Morimoto, Hiroki Takayama, Tomonori Seno, Koichi Takaguchi, Akio Moriya, Hirokazu Miyatake, Ryoichi Okamoto, Kazuhisa Yabushita, Akinobu Takaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   70 ( 1 )   1 - 12   2016年2月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged &gt;= 35 years, HBV DNA &gt;= 4 log copies/mL and positive HBeAg at diagnosis (n = 184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p = 0.013). Among the patients aged &gt;= 35 years with HBV DNA &gt;= 4 log copies/mL and negative HBeAg (n = 237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p &gt; 0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged &gt;= 35 years with HBV DNA &gt;= 4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development.

    DOI: 10.18926/AMO/53996

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  • Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma

    Daisuke Uchida, Akinobu Takaki, Hisashi Ishikawa, Yasuko Tomono, Hironari Kato, Koichiro Tsutsumi, Naofumi Tamaki, Takayuki Maruyama, Takaaki Tomofuji, Ryuichiro Tsuzaki, Tetsuya Yasunaka, Kazuko Koike, Hiroshi Matsushita, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Kazuhiro Nouso, Ryuichi Yoshida, Yuzo Umeda, Susumu Shinoura, Takahito Yagi, Toshiyoshi Fujiwara, Manabu Morita, Masaki Fukushima, Kazuhide Yamamoto, Hiroyuki Okada

    FREE RADICAL RESEARCH   50 ( 7 )   732 - 743   2016年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Background: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model.
    Methods: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy.
    Results: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. L-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers.
    Conclusion: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent L-carnitine is a good candidate to control oxidative stress conditions.

    DOI: 10.3109/10715762.2016.1172071

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  • A case of unresectable combined hepatocellular cholangiocarcinoma showing favorable response to LFP therapy

    Sayuri Kato, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Kenji Kuwaki, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Journal of Japanese Society of Gastroenterology   113 ( 12 )   2050 - 2056   2016年

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    記述言語:日本語   出版者・発行元:Japanese Society of Gastroenterology  

    A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma Therefore, sorafenib was administered
    however, 6 months later, the disease progressed. Consequently, she received second-line chemotherapy with a one-shot intra-arterial injection of cisplatin, but this too was ineffective, and her general condition worsened. As hence, we changed the regimen to 5-fluorouracil continuous infusion and consecutive low dose cisplatin (LFP) therapy. After one cycle of chemotherapy with LFP, Gd-EOB-DTPA-enhanced MRI showed markedly decreased sizes and numbers of tumors. To date, she has completed six cycles of LFP therapy, and almost all her tumors are no longer visible on MRI. She has recovered to a good state and has achieved long-term survival. Thus, this case indicates that although LFP therapy is generally selected for cases of advanced hepatocellular carcinoma, it also appears to be effective for long-term disease control in cases of hepatocellular cholangiocarcinoma.

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  • Low frequency of drug-resistant virus did not affect the therapeutic efficacy in daclatasvir plus asunaprevir therapy in patients with chronic HCV genotype-1 infection

    Hideaki Kinugasa, Fusao Ikeda, Kouichi Takaguchi, Chizuru Mori, Takehiro Matsubara, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Shinichi Toyooka, Kazuhide Yamamoto

    ANTIVIRAL THERAPY   21 ( 1 )   37 - 44   2016年

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    記述言語:英語   出版者・発行元:INT MEDICAL PRESS LTD  

    Background: The efficacy of a direct-acting antiviral agent (DAA) is compromised by the development of drug resistance. The associations between resistance-associated virus (RAV) and therapeutic outcomes have not been well-understood.
    Methods: A total of 30 patients with HCV genotype-1b were enrolled and treated for 24 weeks with asunaprevir (ASV) and daclatasvir (DCV). Viral sequences in non-structural (NS) regions 3 and 5A in serum and liver tissue before treatment were examined with direct sequencing, next-generation sequencing (NGS) and the PCR-invader method to evaluate the importance of drug-resistance in the prediction of the outcomes of ASV plus DCV therapy.
    Results: Of 30 patients (22 treatment-naive patients, 2 interferon-intolerant patients and 6 non-responders), 25 patients (83.3%) achieved sustained virological response (SVR) 24 weeks after the treatment. Viral breakthrough occurred in three treatment-naive patients and one non-responder. One treatment-naive patient experienced viral relapse. Among 25 patients without RAV, 24 obtained SVR, whereas 5 patients had RAV with a 1.3 to 88% frequency, resulting in various therapeutic outcomes. As for HCV compartments, similar RAVs were detected in serum and liver tissue for a patient obtaining SVR despite HCV NS5A Y93H and another developed viral breakthrough although no RAV was detected. Direct sequencing could not detect RAVs in low frequency (1.3 to 12%) for three of four patients.
    Conclusions: Low frequency of RAVs might not affect the outcomes of ASV plus DCV therapy. Deep sequencing and PCR-invader methods can detect clinically significant RAVs for ASV plus DCV therapy.

    DOI: 10.3851/IMP2976

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  • 肝移植医療を地域と大学が一体としてまとめ上げた実績とさらなる発展

    八木孝仁, 篠浦 先, 楳田祐三, 吉田龍一, 信岡大輔, 杭瀬 崇, 渡辺信之, 高木弘誠, 須井健太, 藤原俊義, 高木章乃夫, 吉田真理, 保田裕子, 森松博史

    肝胆膵   72 ( 3 )   481 - 487   2016年

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  • Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis

    Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Motoko Kanzaki, Tomokazu Nunoue, Kazuyuki Hida, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto, Hiroshi Kiyonari, Hirofumi Makino, Jun Wada

    SCIENTIFIC REPORTS   5   2015年11月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity.

    DOI: 10.1038/srep16920

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  • 異なる経過をたどった多発肝転移合併脾臓原発血管肉腫の2例

    脇地 一生, 大西 秀樹, 能祖 一裕, 大山 淳史, 足立 卓哉, 下村 泰之, 和田 望, 森元 裕貴, 安中 幸, 竹内 康人, 安中 哲也, 桑木 健志, 池田 房雄, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   56 ( Suppl.3 )   A1122 - A1122   2015年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • TACE後RFAまでの腫瘍縮小を目指した至適待機期間の探索

    赤穂 宗一郎, 中村 進一郎, 能祖 一裕, 和田 望, 森元 裕貴, 竹内 康人, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 白羽 英則, 高木 章乃夫, 岡田 裕之

    肝臓   56 ( Suppl.3 )   A954 - A954   2015年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 急性肝不全に対する内科的治療と肝移植の現状

    楳田 祐三, 賀来 隆治, 安中 哲也, 篠浦 先, 吉田 龍一, 信岡 大輔, 松崎 孝, 保田 裕子, 高木 章乃夫, 藤原 俊義, 八木 孝仁

    移植   50 ( 4-5 )   477 - 477   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 初回および再肝移植後に脂肪性肝炎を発症した1例

    田中 健大, 田中 顕之, 柳井 広之, 篠浦 先, 楳田 祐三, 吉田 龍一, 高木 章乃夫, 藤原 俊義, 八木 孝仁

    移植   50 ( 4-5 )   551 - 551   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 岡山大学病院ICUにおける急性肝不全に対する肝移植までのBridging Therapyについて

    賀来 隆治, 楳田 祐三, 松崎 孝, 柴田 麻里, 篠浦 先, 吉田 龍一, 信岡 大輔, 保田 裕子, 高木 章乃夫, 八木 孝仁, 森松 博史

    移植   50 ( 4-5 )   477 - 478   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • Serum oxidative-anti-oxidative stress balance is dysregulated in patients with non-alcoholic steatohepatitis and related hepatocellular carcinoma

    Yasuyuki Shimomura, Akinobu Takaki, Nozomu Wada, Daisuke Uchida, Yasuto Takeuchi, Tetsuya Yasunaka, Fusao Ikeda, Hideki Onishi, Kenji Kuwaki, Shinichiro Nakamura, Kazuhiro Nouso, Yasuhiro Miyake, Kazuko Koike

    HEPATOLOGY   62   1297A - 1297A   2015年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma

    Koji Miyahara, Kazuhiro Nouso, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   45 ( 9 )   986 - 993   2015年9月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    AimMost of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application.
    MethodsWe analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters.
    ResultsThe total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (&gt;3), large tumor size (&gt;3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC.
    ConclusionWe demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.

    DOI: 10.1111/hepr.12441

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  • 肝移植術前管理と肝移植後の難治性腹水におけるトルバプタンの有効性

    楳田 祐三, 八木 孝仁, 高木 章乃夫, 篠浦 先, 吉田 龍一, 信岡 大輔, 安中 哲也, 渡辺 信之, 杭瀬 崇, 高木 弘誠, 保田 裕子, 藤原 俊義

    移植   50 ( 総会臨時 )   336 - 336   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 移植医療におけるHCV治療up-to-date 肝移植後C型肝炎における免疫抑制性T細胞とキメリズムの病態への影響

    高木 章乃夫, 内海 方嗣, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 高木 弘誠, 安中 哲也, 保田 裕子, 八木 孝仁

    移植   50 ( 総会臨時 )   207 - 207   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 移植医療人の役割分担と協調はどうあるべきか 外科医、内科医、コーディネーターの関係

    八木 孝仁, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 渡辺 信之, 高木 弘誠, 須井 健太, 木村 祐司, 藤原 俊義, 吉田 真理, 保田 裕子, 高木 章乃夫

    移植   50 ( 総会臨時 )   219 - 219   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • ソラフェニブ治療による長期生存例の検討

    足立 卓哉, 能祖 一裕, 和田 望, 森元 裕貴, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   56 ( Suppl.2 )   A749 - A749   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝臓移植における血管吻合とくに非顕微鏡的肝動脈再建と肝静脈・下大静脈置換の手技

    八木 孝仁, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 杭瀬 崇, 渡辺 信之, 高木 弘誠, 須井 健太, 木村 祐司, 藤原 俊義, 吉田 真理, 保田 裕子, 高木 章乃夫

    移植   50 ( 総会臨時 )   197 - 197   2015年9月

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  • Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence

    Akinobu Takaki, Tetsuya Yasunaka, Takahito Yagi

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   16 ( 8 )   17494 - 17513   2015年8月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MDPI AG  

    Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in &gt;90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is &gt;80% without prevention, while &gt;90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.

    DOI: 10.3390/ijms160817494

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  • 肝移植後の腎機能の経過と降圧療法について

    高木 章乃夫, 八木 孝仁, 保田 裕子, 安中 哲也, 貞森 裕, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 内海 方嗣, 藤原 俊義, 山本 和秀

    移植   50 ( 2-3 )   292 - 292   2015年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 生体肝移植におけるリスク因子としての高齢ドナーと背景疾患との関連性

    楳田 祐三, 高木 弘誠, 杭瀬 崇, 内海 方嗣, 信岡 大輔, 吉田 龍一, 篠浦 先, 保田 裕子, 高木 章乃夫, 藤原 俊義, 八木 孝仁

    移植   50 ( 2-3 )   248 - 249   2015年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • Enhancement of Programmed Death Ligand 2 on Hepatitis C Virus Infected Hepatocytes by Calcineurin Inhibitors

    Kazuko Koike, Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Tetsuya Yasunaka, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Daisuke Nobuoka, Masashi Utsumi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    TRANSPLANTATION   99 ( 7 )   1447 - 1454   2015年7月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background. Post orthotopic liver transplantation (OLT) viral hepatitis is an immunological condition where immune cells induce hepatitis during conditions of immune-suppression. The immune-regulatory programmed death-1 (PD-1)/PD-ligand 1 system is acknowledged to play important roles in immune-mediated diseases. However, the PD-1/PD-L2 interaction is not well characterized, with PD-L2 also exhibiting an immunostimulatory function. We hypothesized that this atypical molecule could affect the recurrence of post-OLT hepatitis. To test this hypothesis, we conducted immunohistochemical staining analysis and in vitro analysis of PD-L2. Methods. The expression of PD-L2 was evaluated in liver biopsy specimens from patients with chronic hepatitis B (n = 15), post-OLT hepatitis B (n = 8), chronic hepatitis C (n = 48), and post-OLT hepatitis C (CH-C-OLT) (n = 14). The effect of calcineurin inhibitors (CNIs) and hepatitis C virus (HCV) on PD-L2 expression was investigated in hepatoma cell lines. Results. The PD-L2 was highly expressed on CH-C-OLT hepatocytes. Treatment of hepatoma cell lines with CNIs resulted in increased PD-L2 expression, especially in combination with HCV core or NS3 protein. Transfection of cell lines with PD-L2 containing plasmid resulted in high intercellular adhesion molecule-1 (ICAM-1) expression, which might enhance hepatitis activity. Conclusions. The PD-L2 is highly expressed on CH-C-OLT hepatocytes, whereas HCV proteins, in combination with CNIs, induce high expression of PD-L2 resulting in elevated expression of ICAM-1. These findings demonstrate the effect of CNIs on inducing PD-L2 and subsequent ICAM-1 expression, effects that may produce inflammatory cell infiltration in post-OLT hepatitis C.

    DOI: 10.1097/TP.0000000000000572

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  • Aberrant Expression of Keratin 7 in Hepatocytes as a Predictive Marker of Rapid Progression to Hepatic Failure in Asymptomatic Primary Biliary Cirrhosis

    Hiroyuki Seki, Fusao Ikeda, Shintaro Nanba, Yuki Moritou, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Minoru Nakamura, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   69 ( 3 )   137 - 144   2015年6月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patients' hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis.

    DOI: 10.18926/AMO/53520

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  • Local Recurrences and Complications After Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis Focused on Tumor Locations

    Junichi Toshimori, Kazuhiro Nouso, Shinichiro Nakamura, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Tetsuya Yasunaka, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S1030 - S1030   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Oxidative Stress Balance Is Dysregulated in Cholangiocarcinoma That Could Be Improved With L-Carnitine Administration

    Daisuke Uchida, Akinobu Takaki, Yasuko Tomono, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S967 - S967   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Alteration of Serum N-Glycan Profile in Patients With Hepatocellular Carcinoma and Their Clinical Application

    Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S1022 - S1022   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • C型慢性肝炎に対するアスナプレビル・ダクラタスビル(第3相治験)の臨床的特徴から看護支援の検討

    難波 志穂子, 池田 房雄, 人部 友, 黒田 智, 千堂 年昭, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   56 ( Suppl.1 )   A505 - A505   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Entecavir Reduces Hepatocarcinogenesis in Patients With Chronic Hepatitis B

    Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S968 - S968   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 腫瘍マーカーの推移から見た肝動注化学療法の早期治療効果予測

    大西 秀樹, 能祖 一裕, 中村 進一郎, 和田 望, 竹内 康人, 桑木 健志, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   56 ( Suppl.1 )   A522 - A522   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Serum N-Glycan Profiles in Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas

    Yutaka Akimoto, Kazuhiro Nouso, Hironari Kato, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Takeshi Tomoda, Naoki Yamamoto, Koichiro Tsutsumi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Shin-ichiro Nishimura, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S518 - S518   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • TLR4, TLR9, and NLRP3 in biliary epithelial cells of primary sclerosing cholangitis: Relationship with clinical characteristics

    Hiroshi Matsushita, Yasuhiro Miyake, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   30 ( 3 )   600 - 608   2015年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and AimInappropriate innate immune responses have been suggested to contribute to the pathogenesis of primary sclerosing cholangitis (PSC). We evaluated the associations of expressions of toll-like receptor (TLR) 4, TLR9, and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in the biliary epithelial cells (BECs) with clinical features of PSC patients.
    MethodsWe retrospectively evaluated the expressions of TLR4, TLR9, and NLRP3 in the intrahepatic BECs by immunohistochemical staining in 21 PSC patients and 10 normal controls. In PSC, 17 patients underwent liver biopsy, and, in the other four patients, liver specimens were obtained at the time of liver transplantation.
    ResultsTLR9 expressions in BECs were higher in PSC patients than in normal controls. TLR9 expressions were correlated with Ludwig fibrosis scores in PSC patients. TLR4 and NLRP3 expressions were similar between PSC patients and normal controls. Seventeen PSC patients undergoing liver biopsy were followed up during a median period of 55.7 months. Four reached to liver transplantation and four developed cholangiocarcinoma. Patients developing cholangiocarcinoma showed lower NLRP3 expressions than the others. Patients reaching to liver transplantation showed higher TLR9 expressions. Expression levels of TLR9 and NLRP3 were not correlated with liver biochemical tests and Mayo risk scores.
    ConclusionsIn PSC, excessive immune responses through TLR9 signaling may be associated with the disease progression. Insufficient immune response through NLRP3 signaling may be associated with the development of cholangiocarcinoma. Evaluation of TLR9 and NLRP3 expressions in BECs may be useful for predicting the prognosis as an auxiliary marker.

    DOI: 10.1111/jgh.12711

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  • REIC/Dkk-3遺伝子導入による肝細胞癌治療の検討

    澤原 大明, 内田 大輔, 白羽 英則, 永原 照也, 岩室 雅也, 片岡 淳朗, 堀口 繁, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌   112 ( 臨増総会 )   A345 - A345   2015年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • Safe and cost-effective control of post-transplantation recurrence of hepatitis B

    Akinobu Takaki, Takahito Yagi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   45 ( 1 )   38 - 47   2015年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-BLACKWELL  

    A combination of hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low-dose HBIG combined with NUC or HBIG-free regimens have been developed. This article reviews recent advances in post-OLT hepatitis B virus (HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self-producing anti-HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost-effectiveness are required. This review advocates a safe and economical approach to controlling post-OLT HBV recurrence.

    DOI: 10.1111/hepr.12368

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  • Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion

    Hideki Onishi, Kazuhiro Nouso, Shinichiro Nakamura, Kuniaki Katsui, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Yasuto Takeuchi, Kenji Kuwaki, Tetsuya Yasunaka, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Yoshiyuki Kobayashi, Kohsaku Sakaguchi, Susumu Kanazawa, Kazuhide Yamamoto

    HEPATOLOGY INTERNATIONAL   9 ( 1 )   105 - 112   2015年1月

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    記述言語:英語   出版者・発行元:SPRINGER  

    The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.
    We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).
    Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p &lt; 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p &lt; 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).
    CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

    DOI: 10.1007/s12072-014-9592-y

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  • Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study

    Masako Terao, Akinobu Takaki, Takayuki Maruyama, Hiroki Oe, Tetsuya Yasunaka, Naofumi Tamaki, Kazufumi Nakamura, Takaaki Tomofuji, Takahito Yagi, Hiroshi Sadamori, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Kazuhiro Nouso, Daisuke Ekuni, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Manabu Morita, Hiroshi Ito, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    INTERNAL MEDICINE   54 ( 22 )   2815 - 2826   2015年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH.
    Methods We recruited patients with decompensated cirrhosis (n = 69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO(2)) &gt;= 15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient &gt;= 25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study.
    Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p = 0.037) and higher oxidative index values (p = 0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p = 0.049). The potential POPH patients exhibited elevated AaDO(2), suggesting the presence of pulmonary shunting.
    Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

    DOI: 10.2169/internalmedicine.54.4889

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  • Liver cirrhosis; Advances in research and clinics

    2015年

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  • 【腸内細菌up to date:今まさに明らかになりつつある全身疾患への影響】 腸内細菌と肝疾患

    Pharma Medica   2015年

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  • Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

    Akinobu Takaki, Kazuhide Yamamoto

    World Journal of Hepatology   7 ( 7 )   968 - 979   2015年

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    記述言語:英語   出版者・発行元:Baishideng Publishing Group Co  

    Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.

    DOI: 10.4254/wjh.v7.i7.968

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  • 肝炎ウイルススクリーニング検査陽性患者に対する検査報告システムの構築による肝臓専門医受診率向上への取り組み

    下村泰之, 池田房雄, 能祖一裕, 高木章乃夫, 渡邊都貴子, 岩月啓氏, 草野展周, 合地 明, 山本和秀

    肝臓   56 ( 4 )   137 - 143   2015年

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  • 門脈圧亢進症の病態と治療 基礎から臨床へ 門脈圧亢進症における心肺機能と酸化ストレスについての検討(共著)

    高木章乃夫, 寺尾正子, 安中哲也, 白羽英則, 中村進一郎, 麻植浩樹, 中村一文, 岡田裕之

    日本門脈圧亢進症学会雑誌   21 ( 3 )   67 - 67   2015年

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  • A multicenter survey of enteroscopy for the diagnosis of intestinal follicular lymphoma.

    Iwamuro M, Okada H, Kawano S, Shiode J, Takenaka R, Imagawa A, Inaba T, Suzuki S, Nishimura M, Mizuno M, Araki M, Mannami T, Ueki T, Kobashi H, Fukatsu H, Tanaka S, Omoto A, Kawai Y, Kitagawa T, Toyokawa T, Takata K, Yoshino T, Takaki A, Yamamoto K

    Oncol Lett.   10 ( 1 )   131 - 136   2015年

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  • Prevention of vagotonia and pain during radiofrequency ablation of liver tumors

    Shinichiro Nakamura, Kazuhiro Nouso, Hideki Onishi, Kenji Kuwaki, Hiroaki Hagihara, Yasuto Takeuchi, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Yoshiyuki Kobayashi, Hidenori Shiraha, Shinichi Ishikawa, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   44 ( 13 )   1367 - 1370   2014年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Radiofrequency ablation (RFA) is frequently used to treat early stage hepatocellular carcinoma. Two of the most cumbersome side-effects of the ablation procedure are intractable pain and vagotonia when deep sedation is not used. We describe local injection of anesthetic into Glisson's sheath as a new technique for overcoming these problems. Lidocaine was injected into Glisson's sheath when radiofrequency ablation of hepatocellular carcinomas, which were located adjacent to Glisson's sheath, could not be continued due to severe pain (n=8) or bradycardia (n=3). In all three patients who showed vagotonia with bradycardia during the ablations, injection of lidocaine prevented bradycardia, allowing completion of the radiofrequency ablation. Pain was reduced in all eight patients who experienced pain during ablation. No side-effects were observed during the procedures. Injection of anesthetic into Glisson's sheath is simple and effective for reducing intractable pain and vagotonia associated with RFA.

    DOI: 10.1111/hepr.12321

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  • Prevention of vagotonia and pain during radiofrequency ablation of liver tumors

    Shinichiro Nakamura, Kazuhiro Nouso, Hideki Onishi, Kenji Kuwaki, Hiroaki Hagihara, Yasuto Takeuchi, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Yoshiyuki Kobayashi, Hidenori Shiraha, Shinichi Ishikawa, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   44 ( 13 )   1367 - 1370   2014年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Radiofrequency ablation (RFA) is frequently used to treat early stage hepatocellular carcinoma. Two of the most cumbersome side-effects of the ablation procedure are intractable pain and vagotonia when deep sedation is not used. We describe local injection of anesthetic into Glisson's sheath as a new technique for overcoming these problems. Lidocaine was injected into Glisson's sheath when radiofrequency ablation of hepatocellular carcinomas, which were located adjacent to Glisson's sheath, could not be continued due to severe pain (n=8) or bradycardia (n=3). In all three patients who showed vagotonia with bradycardia during the ablations, injection of lidocaine prevented bradycardia, allowing completion of the radiofrequency ablation. Pain was reduced in all eight patients who experienced pain during ablation. No side-effects were observed during the procedures. Injection of anesthetic into Glisson's sheath is simple and effective for reducing intractable pain and vagotonia associated with RFA.

    DOI: 10.1111/hepr.12321

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  • Involvement of platelets in extrahepatic metastasis of hepatocellular carcinoma

    Yuki Morimoto, Kazuhiro Nouso, Nozomu Wada, Yasuto Takeuchi, Hideaki Kinugasa, Koji Miyahara, Tetsuya Yasunaka, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   44 ( 14 )   E353 - E359   2014年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    AimRecently, a relationship between platelets and cancer metastasis has been reported. The aim of this study is to elucidate the risk factors for extrahepatic metastasis (EHM), with emphasis on association with platelets in patients, with hepatocellular carcinoma (HCC).
    MethodsWe examined risk factors for EHM in 1613 consecutive, newly diagnosed HCC patients by logistic regression analysis (case-control study). We also examined the factors by Cox proportional hazard model in a retrospective cohort fashion in 803 patients who received non-curative treatment for HCC.
    ResultsIn the case-control study, multivariate analysis revealed that high platelet counts (odds ratio [OR]=4.84; 95% confidence interval [CI]=1.29-29.54; P=0.01), high tumor number and the presence of macroscopic vascular invasion were significantly associated with EHM. In the cohort study, EHM was diagnosed in 71 patients during the study period (mean observation time=23.3 months). On multivariate analysis, high tumor number, high des--carboxyprothrombin (DCP) and Child-Pugh class A were significantly correlated with EHM, and the patients with high platelet counts tended to develop EHM (OR=1.73; 95% CI=0.99-3.14; P=0.055).
    ConclusionHCC patients with high platelet counts, as well as large numbers of tumors, high serum DCP and Child-Pugh class A, are at risk for EHM.

    DOI: 10.1111/hepr.12315

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  • Nursing Support Increases the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C

    Shihoko Namba, Kayoko Miyake, Fusao Ikeda, Tomoko Hazama, Yu Hitobe, Noriko Yamasaki, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   68 ( 5 )   263 - 268   2014年10月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Nursing support might help patients with chronic hepatitis C (CHC) remain in good mental and physical condition during interferon (IFN) therapy. However, the effects of nursing support have not been studied adequately in this context. This case-control study evaluated the effects of nursing support during IFN therapy. Twenty-four CHC patients who received pegylated IFN and ribavirin were enrolled. Nurses advised patients on the maintenance of their mental and physical condition at weekly visits, based on the results of written questionnaires. An additional 24 patients who received IFN therapy without nursing support and who were matched for age, sex, platelet count, viral serogroup and IFN regimen were selected with propensity score matching as controls. The patients with nursing support during IFN therapy achieved higher sustained virological responses (79%) than those without nursing support (58%). Adherence to the IFN and ribavirin regimens at 24 weeks of therapy were slightly higher in the patients with nursing support than those without it, but these differences were not statistically significant. Adherence to ribavirin after 24 weeks of therapy was significantly higher in those with nursing support than those without it (93% and 66%, p = 0.045). These results suggested that nursing support services could contribute to the virological responses of CHC patients by promoting drug-regimen adherence.

    DOI: 10.18926/AMO/52894

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  • Hepatitis C Virus-specific T-cell Response Correlates with Hepatitis Activity and Donor IL28B Genotype Early after Liver Transplantation

    Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Masashi Utsumi, Eiichi Nakayama, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   68 ( 5 )   291 - 302   2014年10月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-gamma) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At &gt; 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

    DOI: 10.18926/AMO/52898

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  • 非B非C肝癌の臨床的特徴

    竹内 康人, 能祖 一裕, 和田 望, 桑木 健志, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   55 ( Suppl.2 )   A633 - A633   2014年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • γ-secretase inhibitorによるNotch経路阻害は膵癌幹細胞を阻害し抗癌剤治療効果を増強する可能性がある

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌   111 ( 臨増大会 )   A951 - A951   2014年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • Prevalence and Outcomes of Acute Hepatitis B in Okayama, Japan, 2006-2010

    Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Sohji Nishina, Masaaki Korenaga, Keisuke Hino, Shin-ichi Fujioka, Toshiya Osawa, Tatsuya Itoshima, Miwa Kawanaka, Gotaro Yamada, Kazuya Kariyama, Hiroki Takayama, Junichi Kubota, Yoichi Morimoto, Takaaki Mizushima, Haruhiko Yamashita, Hiroaki Tanioka, Yuji Negoro, Junichi Toshimori, Haruhiko Kobashi, Atsushi Hirano, Yasuo Itano, Akinobu Takaki, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   68 ( 4 )   243 - 247   2014年8月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HEY were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p &lt; 0.01), among men who had sex with men (100%, p &lt; 0.005), and among patients having sex with unspecified partners (44.8%, p &lt; 0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A.

    DOI: 10.18926/AMO/52790

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  • 【肝胆膵領域の光学医療;一見に如かず】 肝臓領域の腹腔鏡検査 代表的な肝疾患腹腔鏡アトラス(後世に残る図譜として)

    安中 哲也, 池田 房雄, 下村 泰之, 和田 望, 森元 裕貴, 三宅 康広, 白羽 英則, 高木 章乃夫, 能祖 一裕, 岩崎 良章, 山本 和秀

    肝・胆・膵   69 ( 2 )   169 - 176   2014年8月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer (vol 7, pg 840, 2013)

    Shigeru Horiguchi, Hidenori Shiraha, Teruya Nagahara, Jyunnro Kataoka, Masaya Ituamuro, Minoru Matsubara, Shinichi Nishina, Hironari Kato, Akinobu Takaki, Kazuhiro Nouso, Takehiro Tanaka, Koichi Ichimura, Takahito Yagi, Kazuhide Yamamoto

    MOLECULAR ONCOLOGY   8 ( 5 )   1054 - 1054   2014年7月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    DOI: 10.1016/j.molonc.2014.03.007

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  • Frequency of regulatory T-cell and hepatitis C viral antigen-specific immune response in recurrent hepatitis C after liver transplantation

    Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C. Napier, Nobukazu Watanabe, Hiroshi Sadamori, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Eiichi Nakayama, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi

    TRANSPLANT IMMUNOLOGY   31 ( 1 )   33 - 41   2014年6月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Introduction: Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). However, their frequencies and effects on HCV-specific immune responses have not been well investigated.
    Methods: We determined Treg and Tr1 frequencies in OLT patients with hepatitis C and assessed their associations with HCV-specific T cell responses. These patients comprised the following groups: an early post-transplantation group (n = 14); an OLT-chronic active hepatitis C group (n = 14) with active hepatitis C (alanine aminotransferase of &gt; upper limit of normal/positive for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n = 12) without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT-sustained viral response group (n = 6) with sustained viral responses using interferon treatment (negative for HCV-RNA). The frequencies of HCV-specific CD4+ T cells that secreted interferon-gamma were determined by enzyme-linked immunosorbent spot assay (except for the OLT early group).
    Results: Treg and Tr1 frequencies were low during the early post-transplantation period. OLT patients with sustained viral responses had lower Treg frequencies than those with chronic hepatitis C, whereas Tr1 frequencies were significantly reduced in OLT patients with persistently normal alanine aminotransferase levels compared to those with chronic hepatitis C (p &lt; 0.05). Treg frequencies positively correlated with HCV NS3 antigen-specific interferon-gamma responses, which corresponded to HCV clearance.
    Conclusions: Increased Treg frequencies and reduced HCV-NS3 antigen-specific responses recovered after viral eradication in post-OLT chronic hepatitis C patients. Reduced Tr1 frequencies were associated with hepatitis activity control, which may facilitate controlling chronic hepatitis C in patients after OLT. (C) 2014 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.trim.2014.05.006

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  • 膵癌におけるγセクレターゼ阻害剤を用いた幹細胞抑制による抗癌剤増強効果の検討

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    膵臓   29 ( 3 )   553 - 553   2014年6月

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    記述言語:日本語   出版者・発行元:日本膵臓学会  

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  • Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH)

    Akinobu Takaki, Daisuke Kawai, Kazuhide Yamamoto

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   15 ( 5 )   7352 - 7379   2014年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MDPI AG  

    Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL) attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

    DOI: 10.3390/ijms15057352

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  • Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Takahito Yagi, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   29 ( 5 )   973 - 983   2014年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
    MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
    ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
    ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

    DOI: 10.1111/jgh.12501

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  • NASH肝硬変における肝移植後の経過

    高木 章乃夫, 八木 孝仁, 池田 房雄, 保田 裕子, 安中 哲也, 貞森 裕, 篠浦 先, 楳田 祐三, 吉田 龍一, 信岡 大輔, 内海 方嗣, 藤原 俊義, 山本 和秀

    移植   49 ( 1 )   155 - 155   2014年5月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 生体肝移植におけるドナー年齢限界の見極めと個別化治療戦略

    楳田 祐三, 八木 孝仁, 貞森 裕, 高木 章乃夫, 篠浦 先, 吉田 龍一, 信岡 大輔, 内海 方嗣, 保田 裕子, 高木 弘誠, 藤原 俊義

    移植   49 ( 1 )   80 - 81   2014年5月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 再肝移植症例に対する肝腎同時移植経験と、本邦の複数臓器分配におけるMELD scoreのもつ問題点

    八木 孝仁, 信岡 大輔, 篠浦 先, 保田 裕子, 高木 章乃夫, 吉田 龍一, 内海 方嗣, 楳田 祐三, 高木 弘誠, 貞森 裕, 藤原 俊義, 佐藤 大輔

    移植   49 ( 1 )   69 - 70   2014年5月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 劇症肝炎に対する肝移植

    楳田 祐三, 貞森 裕, 高木 章乃夫, 篠浦 先, 吉田 龍一, 信岡 大輔, 内海 方嗣, 高木 弘誠, 保田 裕子, 藤原 俊義, 八木 孝仁

    移植   49 ( 1 )   165 - 165   2014年5月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 肝移植術後における真菌感染症に対する危険因子の解析

    内海 方嗣, 楳田 祐三, 貞森 裕, 篠浦 先, 吉田 龍一, 信岡 大輔, 高木 弘誠, 保田 裕子, 高木 章乃夫, 藤原 俊義, 八木 孝仁

    移植   49 ( 1 )   95 - 95   2014年5月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 肝疾患の病態と糖鎖抗原の意義 網羅的糖鎖解析による肝細胞癌バイオマーカーの検討

    宮原 孝治, 能祖 一裕, 森元 裕貴, 衣笠 秀明, 和田 望, 竹内 康人, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康弘, 中村 進一郎, 白羽 英則, 高木 章乃夫, 天野 麻穂, 西村 紳一郎, 山本 和秀

    肝臓   55 ( Suppl.1 )   A154 - A154   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌におけるNotchシグナル活性化とその治療ターゲットとしての可能性

    白羽 英則, 片岡 淳朗, 堀口 繁, 岩室 雅也, 永原 照也, 内田 大輔, 仁科 慎一, 竹内 康人, 桑木 健志, 大西 秀樹, 中村 進一郎, 高木 章乃夫, 能祖 一裕, 山本 和秀

    肝臓   55 ( Suppl.1 )   A229 - A229   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Efficacy of sorafenib beyond first progression in patients with metastatic hepatocellular carcinoma

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Shouta Iwadou, Yoshiyuki Kobayashi, Koichi Takaguchi, Yoshitaka Takuma, Hiroyuki Takabatake, Kohsaku Sakaguchi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   44 ( 3 )   296 - 301   2014年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Aim
    We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma (HCC) after first progressive disease (PD), and whether it prolongs patients' survival.
    Methods
    The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued (n = 23) and stopped (n = 13) sorafenib at first radiological PD.
    Results
    The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD (P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD (P = 0.012), and this tendency was observed even when the analysis was limited to Child-Pugh class A patients (P = 0.085).
    Conclusion
    Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit.

    DOI: 10.1111/hepr.12123

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  • Efficacy of sorafenib beyond first progression in patients with metastatic hepatocellular carcinoma

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Shouta Iwadou, Yoshiyuki Kobayashi, Koichi Takaguchi, Yoshitaka Takuma, Hiroyuki Takabatake, Kohsaku Sakaguchi, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   44 ( 3 )   296 - 301   2014年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Aim
    We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma (HCC) after first progressive disease (PD), and whether it prolongs patients' survival.
    Methods
    The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued (n = 23) and stopped (n = 13) sorafenib at first radiological PD.
    Results
    The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD (P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD (P = 0.012), and this tendency was observed even when the analysis was limited to Child-Pugh class A patients (P = 0.085).
    Conclusion
    Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit.

    DOI: 10.1111/hepr.12123

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  • γセクレターゼ阻害剤を用いた膵癌幹細胞治療についての検討

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 岩室 雅也, 片岡 淳朗, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌   111 ( 臨増総会 )   A289 - A289   2014年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • Long-term observation of osteomalacia caused by adefovir-induced Fanconi’s syndrome.

    Terasaka T, Ueta E, Ebara H, Waseda K, Hanayama Y, Takaki A, Kawabata T, Sugiyama H, Hidani K, Otsuka F

    Acta Med Okayama.   68 ( 1 )   53 - 56   2014年2月

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    記述言語:英語  

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  • Assessment of health-related quality of life and how it predicts the outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C

    Hiroshi Matsushita, Fusao Ikeda, Yoshiaki Iwasaki, Hiroyuki Seki, Shintaro Nanba, Yasuto Takeuchi, Yuki Moritou, Tetsuya Yasunaka, Hideki Onishi, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   29 ( 2 )   337 - 343   2014年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms.
    Methods: The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey.
    Results: The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score &lt;= 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045).
    Conclusion: HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.

    DOI: 10.1111/jgh.12337

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  • 日本人肝硬変患者における肝肺症候群 -移植前血液ガススクリーニングの結果より-

    岡田早未, 高木章乃夫, 八木孝仁, 安中哲也, 後藤田達洋, 麻植浩樹, 中村一文, 佐藤秀一, 貞森裕, 篠浦先, 楳田祐三, 吉田龍一, 内海方嗣, 信岡大輔, 保田裕子, 池田房雄, 三宅康広, 伊藤浩, 藤原俊義, 山本和秀

    肝臓   55 ( 3 )   143 - 154   2014年

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    記述言語:日本語  

    DOI: 10.2957/kanzo.55.143

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  • A case of fulminant liver failure associated with hepatitis C virus

    Hiromitsu Kanzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Tetsuya Yasunaka, Kazuko Koike, Yasuhiro Miyake, Yoshiaki Iwasaki, Kazuhiro Nouso, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Masashi Utusmi, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    Clinical Journal of Gastroenterology   7 ( 2 )   170 - 174   2014年

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    記述言語:英語   出版者・発行元:Springer-Verlag Tokyo  

    Fulminant hepatitis due to acute hepatitis C virus (HCV) infection is rarely observed. We present a case study of a 21-year-old male patient who developed HCV-associated fulminant hepatitis after receiving steroid pulse therapy for optic neuritis. Despite daily plasmapheresis, the disease progressed to irreversible liver failure with grade 3 hepatic encephalopathy by the 6th day after symptom onset. The patient received a liver transplant on the 8th day. Serum anti-HCV antibody was negative at that time, but became positive on the 12th day. Positive HCV RNA in the serum at admission was reported after transplantation. Positive changes in anti-HCV antibodies and acute hepatitis with massive necrosis in the histology of the explanted liver indicated fulminant hepatitis due to acute HCV infection. Because of severe hepatitis recurrence, he started 12 months of interferon therapy on the 48th day, and obtained sustained virological response. His anti-HCV antibodies became negative again by 1.5 years after cessation of therapy. HCV genomes recovered from the patient's serum on the 7th and 48th days revealed 2 different clones out of 20 clones with 30 % amino acid difference in hypervariable region 1 of HCV second envelope glycoprotein. One of the 2 clones expanded further after liver transplantation. We conclude that early diagnosis of HCV-associated fulminant hepatitis requires the detection of HCV RNA in the serum. Severe hepatitis recurrence after liver transplantation might occur in patients with fulminant hepatitis due to HCV because of its monoclonal expansion. © 2014 Springer.

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  • A case of Wilson's disease with characteristic laparoscopic findings

    Shin-Ichiro Muro, Tetsuya Yasunaka, Nozomu Wada, Yuki Morimoto, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Noso, Hiroaki Iwasaki, Kazuhide Yamamoto

    Clinical Journal of Gastroenterology   7 ( 2 )   175 - 179   2014年

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    記述言語:英語   出版者・発行元:Springer-Verlag Tokyo  

    A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3-10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson's disease. The amount of copper excretion in the urine was 326.6 μg (&gt
    100 μg/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 μg/24 h. Though hepatic copper concentration was 174.5 μg/g wet tissue (&gt
    200 μg/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson's disease. © 2014 Springer.

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  • A case of fulminant liver failure associated with hepatitis C virus

    Hiromitsu Kanzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Tetsuya Yasunaka, Kazuko Koike, Yasuhiro Miyake, Yoshiaki Iwasaki, Kazuhiro Nouso, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Masashi Utusmi, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    Clinical Journal of Gastroenterology   7 ( 2 )   170 - 174   2014年

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    記述言語:英語   出版者・発行元:Springer-Verlag Tokyo  

    Fulminant hepatitis due to acute hepatitis C virus (HCV) infection is rarely observed. We present a case study of a 21-year-old male patient who developed HCV-associated fulminant hepatitis after receiving steroid pulse therapy for optic neuritis. Despite daily plasmapheresis, the disease progressed to irreversible liver failure with grade 3 hepatic encephalopathy by the 6th day after symptom onset. The patient received a liver transplant on the 8th day. Serum anti-HCV antibody was negative at that time, but became positive on the 12th day. Positive HCV RNA in the serum at admission was reported after transplantation. Positive changes in anti-HCV antibodies and acute hepatitis with massive necrosis in the histology of the explanted liver indicated fulminant hepatitis due to acute HCV infection. Because of severe hepatitis recurrence, he started 12 months of interferon therapy on the 48th day, and obtained sustained virological response. His anti-HCV antibodies became negative again by 1.5 years after cessation of therapy. HCV genomes recovered from the patient's serum on the 7th and 48th days revealed 2 different clones out of 20 clones with 30 % amino acid difference in hypervariable region 1 of HCV second envelope glycoprotein. One of the 2 clones expanded further after liver transplantation. We conclude that early diagnosis of HCV-associated fulminant hepatitis requires the detection of HCV RNA in the serum. Severe hepatitis recurrence after liver transplantation might occur in patients with fulminant hepatitis due to HCV because of its monoclonal expansion. © 2014 Springer.

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  • Contradictory immune response in post liver transplantation hepatitis B and C

    Akinobu Takaki, Takahito Yagi, Kazuhide Yamamoto

    International Journal of Inflammation   2014   2014年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:Hindawi Publishing Corporation  

    Hepatitis B and C often progress to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). After OLT, hepatitis B recurrence is clinically controlled with a combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using a HBV envelope antigen vaccine. Patients who had not been HBV carriers such as acutely infected liver failure or who received liver from HBV self-limited donor are good candidate. For chronic HBV carrier patients, a successful response can only be achieved in selected patients such as those treated with experimentally reduced immunosuppression protocols or received an anti-HBV adaptive memory carrying donor liver. Hepatitis C virus (HCV) reinfects transplanted livers at a rate of &gt
    90%. HCV reinfected patients show different severities of hepatitis, from mild and slowly progressing to severe and rapidly progressing, possibly resulting from different adaptive immune responses. More than half the patients require interferon treatment, although the success rate is low and carries risks for leukocytopenia and rejection. Managing the immune response has an important role in controlling recurrent hepatitis C. This study aimed to review the adaptive immune response in post-OLT hepatitis B and C.

    DOI: 10.1155/2014/814760

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  • L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway

    Hisashi Ishikawa, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY   60 ( 7 )   761A - 761A   2014年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Entecavir reduces the incidence of hepatocellular carcinoma in patients with chronic hepatitis B

    Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Tomonori Seno, Koichi Takaguchi, Kazuhide Yamamoto

    HEPATOLOGY   60   1096A - 1096A   2014年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Which patients respond best to hepatitis B vaccination after a hepatitis B virus-related liver transplantation?

    Akinobu Takaki, Takahito Yagi, Tetsuya Yasunaka, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Daisuke Nobuoka, Masashi Utsumi, Yuko Yasuda, Eiichi Nakayama, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    Journal of Gastroenterology   48 ( 12 )   1373 - 1383   2013年12月

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    記述言語:英語  

    Background: A combination of hepatitis B immunoglobulin and nucleos(t)ide analogues is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, frequent immunoglobulin treatment is expensive and inconvenient. This study investigated the efficacy of hepatitis B virus (HBV) vaccination in preventing the recurrence of hepatitis B after living donor OLT. Methods: Twenty-seven patients who had undergone living donor OLT participated in the study
    five had acute HBV infected liver failure (ALF-OLT) and 22 had HBV related liver cirrhosis (LC-OLT). Hepatitis B surface antigen (HBsAg)-containing vaccine was administered to them for at least 1 year after transplantation and continued once monthly for up to 36 months post-OLT. Patients who had anti-HBs antibody titers above 100 mIU/mL for a minimum of 6 months without immunoglobulin administration were defined as good responders
    the others were defined as poor responders. Interferon-γ enzyme-linked immunospot assays against HBs and HBc antigens were used to assay cellular immune responses. Results: All five of the ALF-OLT patients had good responses after a median of four (range 2.5-5) vaccinations. Nine of the 22 LC-OLT patients had good responses after a median of 19 (range 11.5-30) vaccinations. Among the LC-OLT group, those with livers donated by relatively higher-aged, marital and high-titer anti-HBs antibody donors were good responders. LC-OLT patients classed as good responders showed interferon-γ responses comparable to those of the ALF-OLT patients. Conclusions: The ALF-OLT and LC-OLT patients who received livers from relatively higher-aged, marital, high-titer anti-HBs antibody donors were the best candidates for HBV vaccine administration. Boosting donors before transplantation may facilitate later vaccine response of the recipients. © 2013 The Author(s).

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  • Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH)

    Akinobu Takaki, Daisuke Kawai, Kazuhide Yamamoto

    International Journal of Molecular Sciences   14 ( 10 )   20704 - 20728   2013年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. © 2013 by the authors
    licensee MDPI, Basel, Switzerland.

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  • Serum Glycan Markers for Evaluation of Disease Activity and Prediction of Clinical Course in Patients with Ulcerative Colitis

    Koji Miyahara, Kazuhiro Nouso, Shunsuke Saito, Sakiko Hiraoka, Keita Harada, Sakuma Takahashi, Yuki Morimoto, Sayo Kobayashi, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Kazuko Hirose, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    PLoS ONE   8 ( 10 )   e74861-e74861   2013年10月

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    記述言語:英語  

    Background:The aims of this study were to determine the change of whole-serum N-glycan profile in ulcerative colitis (UC) patients and to investigate its clinical utility.Methods:We collected serum from 75 UC patients at the time of admission and the same number of age/sex-matched healthy volunteers. Serum glycan profile was measured by comprehensive quantitative high-throughput glycome analysis and was compared with disease activity and prognosis.Results:Out of 61 glycans detected, 24 were differentially expressed in UC patients. Pathway analysis demonstrated that highly sialylated multi-branched glycans and agalactosyl bi-antennary glycans were elevated in UC patients
    in addition, the glycan ratio m/z 2378/1914, which also increased in UC, showed the highest Area under Receiver Operating Characteristic curve (0.923) for the diagnosis of UC. Highly sialylated multi-branched glycans and the glycan ratio m/z 2378/1914 were higher in the patients with total colitis, Clinical Activity Index &gt
    10, Mayo endoscopic score 3, or a steroid-refractory status. In particular, the glycan ratio m/z 2378/1914 (above median) was an independent prognostic factor for the need for an operation (hazard ratio, 2.67
    95% confidence interval, 1.04-7.84).Conclusions:Whole-serum glycan profiles revealed that the glycan ratio m/z 2378/1914 and highly sialylated multi-branched glycans increase in UC patients, and are correlated with disease activity. The glycan ratio m/z 2378/1914 was an independent predictive factor of the prognosis of UC. © 2013 Miyahara et al.

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  • Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

    K. Miyahara, K. Nouso, Y. Morimoto, Y. Takeuchi, H. Hagihara, K. Kuwaki, H. Onishi, F. Ikeda, Y. Miyake, S. Nakamura, H. Shiraha, A. Takaki, M. Honda, S. Kaneko, T. Sato, S. Sato, S. Obi, S. Iwadou, Y. Kobayashi, K. Takaguchi, K. Kariyama, Y. Takuma, H. Takabatake, K. Yamamoto

    BRITISH JOURNAL OF CANCER   109 ( 8 )   2072 - 2078   2013年10月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Background: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods: In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

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  • Clinical utility of high-throughput glycome analysis in patients with pancreatic cancer

    Kazuhiro Nouso, Maho Amano, Yoichi M. Ito, Koji Miyahara, Yuki Morimoto, Hironari Kato, Koichiro Tsutsumi, Takeshi Tomoda, Naoki Yamamoto, Shinichiro Nakamura, Sayo Kobayashi, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Taku Nakahara, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY   48 ( 10 )   1171 - 1179   2013年10月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility.
    Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters.
    Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p &lt; 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001).
    Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

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  • Serial Changes of Serum Growth Factor Levels and Liver Regeneration after Partial Hepatectomy in Healthy Humans

    Kazuyuki Matsumoto, Yasuhiro Miyake, Yuzo Umeda, Hiroshi Matsushita, Hiroaki Matsuda, Akinobu Takaki, Hiroshi Sadamori, Kazuhiro Nouso, Takahito Yagi, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   14 ( 10 )   20877 - 20889   2013年10月

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    記述言語:英語   出版者・発行元:MDPI AG  

    This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various growth factors before hepatectomy and on postoperative day (POD) 1, 3, 5 and 7 were measured. Liver volume data calculated by multi-detector computed tomography using workstation. The ratio of remnant liver volume on POD 0 to liver volume before the operation was 51% +/- 20%. The ratio of liver volume on POD 14 to liver volume on POD 0 were inversely correlated with remnant liver volume on POD 0 (r = -0.91). The ratio of liver volume on POD 14 to liver volume on POD 0 were significantly correlated with serum hepatocyte growth factor (HGF) levels on POD 1 (r = 0.54), serum leptin levels on POD 1 (r = 0.54), and serum macrophage colony-stimulating factor (M-CSF) levels on POD 5 (r = 0.76) and POD 7 (r = 0.80). These results suggest that early-phase elevation of serum levels of HGF, leptin and M-CSF may be associated with the acceleration of liver regeneration after hepatectomy in humans.

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  • Serum oxidative-anti-oxidative stress balance is dysregulated in patients with hepatitis C virus-related hepatocellular carcinoma

    Mamoru Nishimura, Akinobu Takaki, Naofumi Tamaki, Takayuki Maruyama, Hideki Onishi, Sayo Kobayashi, Kazuhiro Nouso, Tetsuya Yasunaka, Kazuko Koike, Hiroaki Hagihara, Kenji Kuwaki, Shinichiro Nakamura, Fusao Ikeda, Yoshiaki Iwasaki, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto

    Hepatology Research   43 ( 10 )   1078 - 1092   2013年10月

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    記述言語:英語  

    Aim: Oxidative stress is associated with progression of chronic liver disease (CLD). This association is best established in chronic hepatitis C. However, the anti-oxidative state is not well characterized. The objective of the present study was to investigate the balance of oxidative and anti-oxidative stress in CLD patients. Methods: We recruited a study population of 208 patients, including healthy volunteers (HV
    n=15), patients with hepatitis B virus (HBV)-related CLD without or with hepatocellular carcinoma (HBV-non-HCC, n=25, and HBV-HCC, n=50, respectively), and patients with hepatitis C virus (HCV)-related CLD without or with HCC (HCV-non-HCC, n=49, and HCV-HCC, n=69, respectively). Serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY-adsorbent test
    OXY) were determined, and the balance of these values was used as the oxidative index. Correlations among ROM, OXY, oxidative index and clinical characteristics were investigated. Results: Patients with CLD exhibited elevated ROM and oxidative index compared to HV. Among patients with CLD, HCV positive status correlated with increased ROM. In CLD, HCV-HCC patients exhibited the highest ROM levels. Among HCV-related CLD patients, lower OXY correlated with HCC positive status, but was recovered by eradication of HCC. In HCV-HCC, lower OXY correlated with high PT-INR. Conclusion: HCV positive CLD patients displayed higher oxidative stress and HCV-HCC patients displayed lower anti-oxidative state. Anti-oxidative state depression was associated with liver reservoir-related data in HCV-HCC and could be reversed with HCC eradication. © 2012 The Japan Society of Hepatology.

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  • Evaluation of the effect of sorafenib using serum NX-des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma

    Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Takeshi Tomoda, Sayo Kobayashi, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Ohnishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   43 ( 10 )   1064 - 1070   2013年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    AimDes--carboxyprothrombin (DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma (HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX-DCP, which is specific to vitamin K absence.
    MethodsSerum DCP and NX-DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines.
    ResultsDCP and NX-DCP increased 1.58- (median, range 0.21-28.7) and 1.20-fold (median, range 0.41-14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low-elevation group). However, 12 patients showed over twofold increase of both DCP and NX-DCP (double-elevation group), and eight patients showed over twofold increase of DCP alone (DCP-elevation group). The disease control rate (DCR) of the DCP-elevation group (12.5%) was significantly lower than those of the double-elevation group (75.0%, P=0.020) and the low-elevation group (60.0%, P=0.042). Progression-free survival (PFS) was significantly shorter in the DCP-elevation group than in the double-elevation group (P=0.006) and the low-elevation group (P=0.001).
    ConclusionNX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.

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  • Strong hepatitis C virus-specific T-cell immune responses correlate with lower hepatitis activities and donor IL28B major genotype in the early period after living donor liver transplantation

    Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hirsohi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Masashi Utsumi, Daisuke Nobuoka, Toshiyoshi Fujiwara, Kazuhide Yamamoto

    HEPATOLOGY   58   1048A - 1048A   2013年10月

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  • Nucleoside analogue treatment can not reduce the incidence of hepatocellular carcinoma in patients with chronic hepatitis B

    Tetsuya Yasunaka, Fusao Ikeda, Nozomu Wada, Yuuki Morimoto, Kenji Kuwaki, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY   58   671A - 671A   2013年10月

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  • Frequency of regulatory T cell and HCV antigen specific immune response in recurrent hepatitis C after liver transplantation

    Akinobu Takaki, Masashi Utsumi, Kazuko Koike, Takahito Yagi, Nobukazu Watanabe, Ryuichiro Tsuzaki, Hirsohi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Hidenori Shiraha, Kazuhide Yamamoto

    HEPATOLOGY   58   1178A - 1178A   2013年10月

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  • Prediction of Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib by Comprehensive Serum Glycan Analysis

    Kazuhiro Nouso, Koji Miyahara, Yuuki Morimoto, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Koichi Takaguchi, Takahisa Sato, Shinpei Sato, Shuntaro Obi, Kazuko Hirose, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

    HEPATOLOGY   58   1242A - 1242A   2013年10月

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  • Predictive impacts of alpha-fetoprotein levels on development of hepatocellular carcinoma during interferon therapy for chronic hepatitis C

    Yasuto Takeuchi, Fusao Ikeda, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto

    HEPATOLOGY   58   1128A - 1129A   2013年10月

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  • 肝細胞癌遠隔転移と血小板の関係

    森元 裕貴, 能祖 一裕, 和田 望, 竹内 康人, 宮原 孝治, 萩原 宏明, 桑木 健志, 安中 哲也, 大西 秀樹, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   54 ( Suppl.2 )   A638 - A638   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • TACE不応症例への治療戦略の検討

    和田 望, 能祖 一裕, 中村 進一郎, 森元 裕貴, 竹内 康人, 安中 哲也, 萩原 宏明, 桑木 健志, 大西 秀樹, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   54 ( Suppl.2 )   A641 - A641   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Prognotic impact of serum follistatin in patients with hepatocellular carcinoma

    Takeshi Tomoda, Kazuhiro Nouso, Koji Miyahara, Sayo Kobayashi, Hideaki Kinugasa, Junki Toyosawa, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   28 ( 8 )   1391 - 1396   2013年8月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Follistatin (FST) is a glycoprotein expressed in most organs, which interacts with activins or other members of the transforming growth factor beta family. Recently, several reports have shown that FST regulates a variety of processes during tumor progression. Here, serum FST in patients with liver diseases was measured, and its clinical utility as a biomarker was assessed.
    Methods: Serum was collected from 162 patients (91 hepatocellular carcinoma [HCC], 43 liver cirrhosis, and 28 chronic hepatitis) as well as from 16 healthy volunteers. FST was quantified by enzyme-linked immunosorbent assays, and levels were compared with clinical parameters including survival of the HCC patients.
    Results: Median serum FST levels in HCC, liver cirrhosis, chronic hepatitis, and healthy volunteers were 1168, 1606, 1324, and 1661 pg/mL, respectively, not significantly different. In HCC patients, higher serum FST was associated with greater age, hepatitis C virus antibody-negativity, large tumor size, g-glutamyl transpeptidase, des-gamma carboxyprothrombin and presence of portal vein tumor thrombus. Survival of HCC patients with high FST levels was significantly shorter than for those with low levels (P = 0.004). Multivariate analysis revealed that in addition to large tumor size and presence of portal vein thrombus, high FST levels were independently correlated with poor prognosis (hazard ratio = 2.41, 95% confidence interval = 1.16-5.00, P = 0.02).
    Conclusions: Serum FST levels are significantly associated with HCC prognosis and could represent a predictive biomarker in this disease.

    DOI: 10.1111/jgh.12167

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  • 移植医療における看護師が抱える倫理的ジレンマ 遺伝性疾患に対する肝移植におけるレシピエント移植コーディネーターのあり方

    保田 裕子, 安中 哲也, 楳田 祐三, 高木 章乃夫, 八木 孝仁

    移植   48 ( 総会臨時 )   267 - 267   2013年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • アルコール性肝硬変患者に対する肝移植適応基準確立に向けた岡山大学病院での取組み

    吉田 龍一, 高木 弘誠, 内海 方嗣, 信岡 大輔, 楳田 祐三, 篠浦 先, 貞森 裕, 保田 裕子, 高木 章乃夫, 藤原 俊義, 八木 孝仁

    移植   48 ( 総会臨時 )   309 - 309   2013年8月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 法改正後の肝移植紹介患者の経過より分かる現状の生体と脳死の選択

    高木 章乃夫, 保田 裕子, 八木 孝仁, 安中 哲也, 貞森 裕, 篠浦 先, 楳田 祐三, 白羽 英則, 能祖 一裕, 藤原 俊義, 山本 和秀

    日本門脈圧亢進症学会雑誌   19 ( 3 )   184 - 184   2013年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • カルニチン及びビタミンE投与による酸化ストレスとNASH病態改善の関連

    石川 久, 高木 章乃夫, 松下 浩志, 津崎 龍一郎, 小池 和子, 三宅 康広, 白羽 英則, 山本 和秀

    肝臓   54 ( Suppl.1 )   A389 - A389   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • ソラフェニブ中止に伴う腫瘍進展に関する検討

    宮原 孝治, 能祖 一裕, 森元 裕貴, 竹内 康人, 和田 望, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   54 ( Suppl.1 )   A115 - A115   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌におけるRUNX3発現低下はNotchシグナルを介し癌幹細胞化とEMTを制御する

    白羽 英則, 片岡 淳朗, 堀口 繁, 岩室 雅也, 永原 照也, 内田 大輔, 仁科 慎一, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓   54 ( Suppl.1 )   A151 - A151   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis

    Yasuto Takeuchi, Fusao Ikeda, Yuki Moritou, Hiroaki Hagihara, Tetsuya Yasunaka, Kenji Kuwaki, Yasuhiro Miyake, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Yoshiaki Iwasaki, Kazuhiro Nouso, Kazuhide Yamamoto

    Journal of Gastroenterology   48 ( 3 )   405 - 412   2013年3月

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    記述言語:英語  

    Background The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with nonalcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. Methods We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). Results NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P&lt
    0.001 and &lt
    0.001, respectively
    log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P&lt
    0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028). Conclusions The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients. © Springer 2012.

    DOI: 10.1007/s00535-012-0647-3

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  • 肝癌EMTマーカーとしてのPIVKA-II

    白羽 英則, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 内田 大輔, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    日本消化器病学会雑誌   110 ( 臨増総会 )   A387 - A387   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • RUNX3欠失はmultidrug resistant protein発現を介してgemcitabine感受性に影響を与える

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 片岡 淳朗, 岩室 雅也, 松原 稔, 加藤 博也, 高木 章乃夫, 能祖 一裕, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌   110 ( 臨増総会 )   A210 - A210   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 原発性硬化性胆管炎の病態における自然免疫の関与

    松下 浩志, 三宅 康広, 山本 和秀, 池田 房雄, 小池 和子, 白羽 英則, 高木 章乃夫, 能祖 一裕

    日本消化器病学会雑誌   110 ( 臨増総会 )   A339 - A339   2013年2月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 貧血を契機に発見され肝硬変に至っていた小児自己免疫性肝炎の1例

    室 信一郎, 安中 哲也, 森元 裕貴, 池田 房雄, 白羽 英則, 高木 章乃夫, 能祖 一裕, 山本 和秀

    肝臓   54 ( 10 )   698 - 704   2013年

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    記述言語:日本語  

    DOI: 10.2957/kanzo.54.698

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  • 8.NASHに対する水素分子の有用性

    高木章乃夫, 山本和秀

    Hepatology Practice第二巻   2 ( 2 )   376 - 379   2013年

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  • Nashに対する水素分子の有用性

    河合 大介, 高木 章乃夫, 山本 和秀

    岡山医学会雑誌   125 ( 3 )   201 - 204   2013年

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  • Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer

    Shigeru Horiguchi, Hidenori Shiraha, Teruya Nagahara, Jyunnro Kataoka, Masaya Iwamuro, Minoru Matsubara, Shinichi Nishina, Hironari Kato, Akinobu Takaki, Kazuhiro Nouso, Takehiro Tanaka, Koichi Ichimura, Takahito Yagi, Kazuhide Yamamoto

    Molecular Oncology   7 ( 4 )   840 - 849   2013年

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    記述言語:英語   出版者・発行元:John Wiley and Sons Ltd  

    Background &amp
    Aim: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer. Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000mg/m2 gemcitabine after the surgery. The pancreatic cancer cell lines PANC-1, MIAPaCa-2, BxPC-3, SUIT-2, and KLM-1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay. Results: Patients with RUNX3-positive and RUNX3-negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3-negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3-positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3-negative cells. Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. © 2013 Federation of European Biochemical Societies.

    DOI: 10.1016/j.molonc.2013.04.004

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  • Risk factors for acute renal injury in living donor liver transplantation: evaluation of the RIFLE criteria.

    Utsumi M, Umeda Y, Sadamori H, Nagasaka T, Takaki A, Matsuda H, Shinoura S, Yoshida R, Nobuoka D, Satoh D, Fuji T, Yagi T, Fujiwara T

    Transpl Int   2013年

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  • A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes

    Masaya Iwamuro, Hidenori Shiraha, Shuhei Nakaji, Masumi Furutani, Naoya Kobayashi, Akinobu Takaki, Kazuhide Yamamoto

    BIOMEDICAL ENGINEERING ONLINE   11   e93-e93   2012年12月

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    記述言語:英語   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Bioartificial liver systems, designed to support patients with liver failure, are composed of bioreactors and functional hepatocytes. Immunological rejection of the embedded hepatocytes by the host immune system is a serious concern that crucially degrades the performance of the device. Induced pluripotent stem (iPS) cells are considered a desirable source for bioartificial liver systems, because patient-derived iPS cells are free from immunological rejection. The purpose of this paper was to test the feasibility of a bioartificial liver system with iPS cell-derived hepatocyte-like cells.
    Methods: Mouse iPS cells were differentiated into hepatocyte-like cells by a multi-step differentiation protocol via embryoid bodies and definitive endoderm. Differentiation of iPS cells was evaluated by morphology, PCR assay, and functional assays. iPS cell-derived hepatocyte-like cells were cultured in a bioreactor module with a pore size of 0.2 mu m for 7 days. The amount of albumin secreted into the circulating medium was analyzed by ELISA. Additionally, after a 7-day culture in a bioreactor module, cells were observed by a scanning electron microscope.
    Results: At the final stage of the differentiation program, iPS cells changed their morphology to a polygonal shape with two nucleoli and enriched cytoplasmic granules. Transmission electron microscope analysis revealed their polygonal shape, glycogen deposition in the cytoplasm, microvilli on their surfaces, and a duct-like arrangement. PCR analysis showed increased expression of albumin mRNA over the course of the differentiation program. Albumin and urea production was also observed. iPS-Heps culture in bioreactor modules showed the accumulation of albumin in the medium for up to 7 days. Scanning electron microscopy revealed the attachment of cell clusters to the hollow fibers of the module. These results indicated that iPS cells were differentiated into hepatocyte-like cells after culture for 7 days in a bioreactor module with a pore size of 0.2 mu m.
    Conclusion: We consider the combination of a bioreactor module with a 0.2-mu m pore membrane and embedded hepatocytes differentiated from iPS cells to be a promising option for bioartificial liver systems. This paper provides the basic concept and preliminary data for an iPS cell-oriented bioartificial liver system. PACS code: 87. Biological and medical physics, 87.85.-d Biomedical engineering, 87.85.Lf Tissue engineering, 87.85.Tu Modeling biomedical systems.

    DOI: 10.1186/1475-925X-11-93

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  • Eradication of Hepatitis C Virus Subgenomic Replicon by Interferon Results in Aberrant Retinol-Related Protein Expression

    Kazuko Koike, Akinobu Takaki, Nobuyuki Kato, Mamoru Ouchida, Hirotaka Kanzaki, Tetsuya Yasunaka, Hidenori Shiraha, Yasuhiro Miyake, Kazuhide Yamamoto

    ACTA MEDICA OKAYAMA   66 ( 6 )   461 - 468   2012年12月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Hepatitis C virus (HOT) infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE) and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their "cured" cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1), which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP), which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression.

    DOI: 10.18926/AMO/49042

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  • Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma

    Shigetomi Tanaka, Hidenori Shiraha, Yutaka Nakanishi, Shin-Ichi Nishina, Minoru Matsubara, Shigeru Horiguchi, Nobuyuki Takaoka, Masaya Iwamuro, Junro Kataoka, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

    INTERNATIONAL JOURNAL OF CANCER   131 ( 11 )   2537 - 2546   2012年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

    DOI: 10.1002/ijc.27575

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  • Clinical utility of serum fucosylated hemopexin in Japanese patients with hepatocellular carcinoma

    Sayo Kobayashi, Kazuhiro Nouso, Hideaki Kinugasa, Yasuto Takeuchi, Takeshi Tomoda, Koji Miyahara, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   42 ( 12 )   1187 - 1195   2012年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Aim: Hepatocellular carcinoma (HCC) is a common clinical problem all over the world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the diagnosis of HCC, however, its clinical implications are unclear. The aim of this study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with HCC.
    Methods: The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85 with chronic hepatitis (CH) and 22 healthy people were examined for the expression of Fuc-Hpx; the level was compared with clinical parameters as well as hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and corresponding adjacent non-cancerous liver tissues were also examined.
    Results: No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6 AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P &lt; 0.001; LC vs HCC, P = 0.02). Multivariate analysis revealed that low albumin, low prothrombin time and the presence of HCC were significantly correlated with high Fuc-Hpx (P = 0.013, =0.001 and &lt;0.001, respectively). Among the HCC patients, albumin was correlated with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc-Hpx in cancer tissue was not different from that in non-cancerous tissue.
    Conclusion: Fuc-Hpx is a valuable biomarker for HCC but it might be a marker for hypercarcinogenic liver rather than a marker for tumor-bearing liver.

    DOI: 10.1111/j.1872-034X.2012.01044.x

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  • Low peripheral blood treg and high HCV specific interferon gamma production achieved after eradication of HCV after liver transplantation

    Kazuko Koike, Akinobu Takaki, Masashi Utsumi, Tetsuya Yasunaka, Yasuhiro Miyake, Takahiro Yagi, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   27   275 - 275   2012年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

    Masaya Iwamuro, Hiroyuki Okada, Katsuyoshi Takata, Katsuji Shinagawa, Shigeatsu Fujiki, Junji Shiode, Atsushi Imagawa, Masashi Araki, Toshiaki Morito, Mamoru Nishimura, Motowo Mizuno, Tomoki Inaba, Seiyu Suzuki, Yoshinari Kawai, Tadashi Yoshino, Yoshiro Kawahara, Akinobu Takaki, Kazuhide Yamamoto

    WORLD JOURNAL OF GASTROENTEROLOGY   18 ( 44 )   6427 - 6436   2012年11月

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    記述言語:英語   出版者・発行元:BAISHIDENG PUBL GRP CO LTD  

    AIM: To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.
    METHODS: This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk.
    RESULTS: Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 +/- 2.4 years vs 60.1 +/- 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/ partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages I E and II E/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 +/- 78 vs 402 +/- 83, P = 0.884), LDH levels (188 +/- 7 vs 183 +/- 8, P = 0.749), hemoglobin levels (13.5 +/- 0.3 vs 12.8 +/- 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1110, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case.
    CONCLUSION: These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required. (C) 2012 Baishideng. All rights reserved.

    DOI: 10.3748/wjg.v18.i44.6427

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  • Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine: A 5-year study of patients with hepatitis B with lamivudine resistance

    Fusao Ikeda, Nobuyuki Baba, Koichi Takaguchi, Junichi Kubota, Kenji Miyoshi, Shin-ichi Fujioka, Yuki Moritou, Yasuto Takeuchi, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

    JOURNAL OF MEDICAL VIROLOGY   84 ( 10 )   1562 - 1570   2012年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.08.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P?=?0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R?=?-0.38, P?=?0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV. J. Med. Virol. 84:15621570, 2012. (c) 2012 Wiley Periodicals, Inc.

    DOI: 10.1002/jmv.23371

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  • Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma

    Minoru Matsubara, Hidenori Shiraha, Jyunro Kataoka, Masaya Iwamuro, Shigeru Horiguchi, Shin-ichi Nishina, Nobuyuki Takaoka, Masayuki Uemura, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   27 ( 10 )   1602 - 1608   2012年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-?-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, P &lt; 0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r = 0.48, P &lt; 0.0001). Conclusions: des-?-carboxyl prothrombin production is associated with tumor angiogenesis in HCC.

    DOI: 10.1111/j.1440-1746.2012.07173.x

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  • Peritoneovenous shunting for refractory ascites results in worsening of nephrotic syndrome

    Akinobu Takaki, Yohei Maeshima, Takahito Yagi, Akihiro Katayama, Norikazu Hinamoto, Shigeru Akagi, Hitoshi Sugiyama, Takeshi Tomoda, Yoshiaki Iwasaki, Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Haruhiko Kobashi, Atsushi Hirano, Hirofumi Makino, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   42 ( 10 )   1048 - 1053   2012年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Peritoneovenous shunt (PVS) is accepted as a treatment for refractory ascites due to liver cirrhosis. Infection is a well-known complication of shunting. However, the effects of PVS in terms of complications for renal disease are unclear. We encountered a case involving a 52-year-old man with alcoholic liver cirrhosis and complications of nephrotic syndrome that were worsened by PVS. He received PVS for refractory ascites due to alcoholic liver cirrhosis before coming to our hospital for evaluation for liver transplantation. Nephrotic syndrome was then identified due to cirrhosis-related membranoproliferative glomerulonephritis (MPGN). Prednisolone was administrated at 60 mg/day for MPGN. On day 5, he showed grade IV hepatic encephalopathy (West Haven criteria). Tapering prednisolone and intestinal cleansing with lactulose treatment improved hepatic encephalopathy, but hyperammonemia persisted and the PVS was removed. After shunt removal, urinary protein levels decreased from 46 g/day to 0.30.5 g/day and ammonia levels decreased. PVS may increase the excretion of urinary protein and increase ammonia levels in patients with complications of glomerulonephritis.

    DOI: 10.1111/j.1872-034X.2012.01012.x

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  • Low frequency of Tr1 in peripheral blood correlated with persistent normal ALT in chronic hepatitis C after liver transplantation

    Akinobu Takaki, Kazuko Koike, Masashi Utsumi, Takahito Yagi, Hirsohi Sadamori, Tetsuya Yasunaka, Kazuhide Yamamoto

    HEPATOLOGY   56   527A - 528A   2012年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • Laparoscopic Findings of Reddish Markings Predict Hepatocellular Carcinoma in HBeAg Positive Chronic Hepatitis B Patients

    Tetsuya Yasunaka, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Shin-ichi Fujioka, Haruhiko Kobashi, Kazuhide Yamamoto

    AMERICAN JOURNAL OF GASTROENTEROLOGY   107   S145 - S145   2012年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:NATURE PUBLISHING GROUP  

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  • Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice

    Daisuke Kawai, Akinobu Takaki, Atsuko Nakatsuka, Jun Wada, Naofumi Tamaki, Tetsuya Yasunaka, Kazuko Koike, Ryuichiro Tsuzaki, Kazuyuki Matsumoto, Yasuhiro Miyake, Hidenori Shiraha, Manabu Morita, Hirofumi Makino, Kazuhide Yamamoto

    HEPATOLOGY   56 ( 3 )   912 - 921   2012年9月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-cholinedeficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-a, interleukin-6, fatty acid synthesisrelated genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL)positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-a expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups. Conclusion: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912921)

    DOI: 10.1002/hep.25782

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  • Diagnostic usefulness of precise examinations with intraductal ultrasonography, peroral cholangioscopy and laparoscopy of immunoglobulin G4-related sclerosing cholangitis

    Shigeru Horiguchi, Fusao Ikeda, Hidenori Shiraha, Naoki Yamamoto, Ichiro Sakakihara, Yasuhiro Noma, Koichiro Tsutsumi, Hironari Kato, Hiroaki Hagihara, Tetsuya Yasunaka, Shinichiro Nakamura, Haruhiko Kobashi, Hirofumi Kawamoto, Kazuhide Yamamoto

    DIGESTIVE ENDOSCOPY   24 ( 5 )   370 - 373   2012年9月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Herein, a case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis is reported. IgG4 was diagnosed based on observations from peroral cholangioscopy and laparoscopy, and these methods are proposed for definitive and precise diagnosis of this disease. A 76-year-old male patient with inguinal Paget's disease had intrahepatic bile duct dilatations detected with computed tomography at his periodic check-up. Magnetic resonance cholangiography showed stenosis of the upper common bile duct and poststenotic dilatation of left intrahepatic bile ducts. The portal tract and bilateral intrahepatic bile ducts were surrounded by a low-density area, facing a tumor-like lesion at segment 2. Cytological examinations of the stenotic and dilated lesions revealed no cellular atypia. Histological examination of the tumor showed normal liver tissue with infiltration of lymphocytes, indicating an inflammatory pseudotumor. Peroral cholangioscopy excluded the possibility of biliary cancer and indicated that the stenotic legion was of submucosal, not mucosal, origin. Laparoscopic observations showed discoloration with wide yellowish-white lobular markings and wide depressed lesions at segments 2 and 7. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. Serum IgG4 levels were elevated. From these findings, the patient was diagnosed with IgG4-related sclerosing cholangitis. After treatment with prednisolone, blood liver enzymes and IgG4 rapidly normalized, bile duct dilatations improved, and the hepatic pseudotumor disappeared. The cholangitis did not recur. In this case, biliary cancer was ruled out by observation with peroral cholangioscopy, and the spread of cholangitis in the liver periphery was verified with laparoscopy; this information could not be obtained with other modalities.

    DOI: 10.1111/j.1443-1661.2012.01300.x

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  • 非B非C肝癌の予後及び特徴

    竹内 康人, 能祖 一裕, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 中村 進一郎, 白羽 英則, 三宅 康広, 高木 章乃夫, 山本 和秀

    肝臓   53 ( Suppl.2 )   A765 - A765   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型肝炎ウイルスに対して免疫寛容状態にある移植後患者でのHBVワクチンの効果

    高木 章乃夫, 八木 孝仁, 安中 哲也, 貞森 裕, 篠浦 先, 楳田 祐三, 保田 裕子, 山本 和秀

    移植   47 ( 総会臨時 )   264 - 264   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • Streptozotocin投与NASH発癌モデルマウスにおける病態進行と水素水投与の有効性の検討

    河合 大介, 高木 章乃夫, 山本 和秀, 中司 敦子, 和田 淳, 玉木 直文, 安中 哲也, 小池 和子, 津崎 龍一郎, 松本 和幸, 三宅 康広, 白羽 英則, 森田 学, 槇野 博史

    日本消化器病学会雑誌   109 ( 臨増大会 )   A708 - A708   2012年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 改正臓器移植法後の脳死肝移植の現状と問題点

    楳田 祐三, 八木 孝仁, 貞森 裕, 高木 章乃夫, 篠浦 先, 吉田 龍一, 信岡 大輔, 佐藤 太祐, 内海 方嗣, 保田 裕子, 藤原 俊義

    移植   47 ( 総会臨時 )   254 - 254   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 移植後B型肝炎に対するHBVワクチンの有用性についての検討

    高木 章乃夫, 八木 孝仁, 安中 哲也, 貞森 裕, 小池 和子, 篠浦 先, 楳田 祐三, 吉田 龍一, 佐藤 太祐, 信岡 大輔, 内海 方嗣, 吉田 一博, 三宅 康広, 保田 裕子, 藤原 俊義, 山本 和秀

    移植   47 ( 4-5 )   341 - 341   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 当院における肝細胞癌に対する生体肝移植症例の検討

    高木 章乃夫, 八木 孝仁, 貞森 裕, 安中 哲也, 篠浦 先, 楳田 祐三, 吉田 龍一, 佐藤 太祐, 信岡 大輔, 内海 方嗣, 中村 進一郎, 能祖 一裕, 保田 裕子, 三浦 公, 藤原 俊義, 山本 和秀

    移植   47 ( 4-5 )   340 - 340   2012年9月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 当院における急性・慢性肝不全に対する脳死肝移植の現状

    安中 哲也, 高木 章乃夫, 保田 裕子, 八木 孝仁, 吉田 龍一, 楳田 祐三, 三宅 康広, 篠浦 先, 貞森 裕, 山本 和秀

    日本門脈圧亢進症学会雑誌   18 ( 3 )   157 - 157   2012年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 膵癌において、CD44の発現は、RUNX3発現は逆相関する(CD44 expression correlates negatively with runt-related transcription factor 3 in pancreatic ductal adenocarcinoma)

    堀口 繁, 白羽 英則, 内田 大輔, 永原 照也, 岩室 雅也, 片岡 淳朗, 加藤 博也, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本癌学会総会記事   71回   179 - 180   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 臓器移植法案改正後、急性肝不全に対する肝移植適応はどう変わったか? 当院における急性肝不全に対する脳死肝移植の現状

    安中 哲也, 高木 章乃夫, 保田 裕子, 八木 孝仁, 吉田 龍一, 楳田 祐三, 三宅 康広, 篠浦 先, 貞森 裕, 山本 和秀

    肝臓   53 ( 7 )   449 - 450   2012年7月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Hepatitis B Vaccine Repeat After Liver Transplantation Succeeds in Type-B Cirrhotics With Marital, High-Hbs-Antibody Donors

    Akinobu Takaki, Takahito Yagi, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Masashi Utsumi, Tetsuya Yasunaka, Kazuhide Yamamoto

    GASTROENTEROLOGY   142 ( 5 )   S998 - S998   2012年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma

    Hideaki Kinugasa, Kazuhiro Nouso, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Shin-ichiro Nakamura, Hidenori Shiraha, Kenji Kuwaki, Hiroaki Hagihara, Fusao Ikeda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY   47 ( 4 )   421 - 426   2012年4月

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    記述言語:英語   出版者・発行元:SPRINGER TOKYO  

    Radiofrequency ablation (RFA) is a standard therapy for the treatment of hepatocellular carcinoma (HCC) with 3 or fewer tumors of up to 3 cm (early-stage HCC); when RFA is unsuccessful or unfeasible, transcatheter arterial chemoembolization (TACE) has often been performed. However, little information about the outcome of TACE for early-stage HCC has been reported and it is hard to decide whether to perform additional treatment following TACE in these difficult conditions. The aim of this study was to determine the risk factors for local or intrahepatic distant recurrence after TACE in early-stage HCC.
    Among 1,560 newly diagnosed HCC patients who were admitted to Okayama University Hospital, 43 patients with early-stage HCC who received only TACE in at least one nodule were enrolled in this study. We analyzed the risk factors for local and distant recurrence by the Cox proportional hazard model.
    The local recurrence rates and intrahepatic distant recurrence rates at 3 months, 6 months, and 1 year were 18.6, 33.4, and 61.8%, and 2.8, 2.8, and 10.2%, respectively. Among 12 parameters examined as possible risk factors for recurrence, heterogeneous Lipiodol uptake (risk ratio 3.38; 95% confidence interval 1.14-10.60) and high serum des-gamma-carboxy prothrombin (DCP) (2.58; 1.03-7.14) were significantly correlated with local recurrence, and the presence of multiple tumors (10.64; 1.76-93.75) was significantly correlated with intrahepatic distant recurrence.
    Heterogeneous Lipiodol uptake, high serum DCP, and multiple tumors are risk factors for recurrence in patients with early-stage HCC who have undergone palliative TACE.

    DOI: 10.1007/s00535-011-0492-9

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  • 肝癌臨床 HCV関連肝細胞癌の遺伝子学的成因についての検討

    竹内 康人, 池田 房雄, 森藤 由記, 萩原 宏明, 安中 哲也, 桑木 健志, 三宅 康広, 大西 秀樹, 中村 進一郎, 白羽 英則, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 山本 和秀

    肝臓   53 ( Suppl.1 )   A263 - A263   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型肝炎 腹腔鏡検査での赤色紋理は、B型慢性肝炎の肝発癌危険因子である

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 藤岡 真一, 小橋 春彦, 山本 和秀

    肝臓   53 ( Suppl.1 )   A326 - A326   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌基礎 肝細胞癌において、カルボキシラーゼ活性低下は、SPARC発現を誘導し、細胞接着低下、EMT進行を引き起こす

    白羽 英則, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓   53 ( Suppl.1 )   A232 - A232   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Streptozotocin投与NASHモデルマウスにおける病態進行と水素水投与の有効性の検討

    河合 大介, 高木 章乃夫, 山本 和秀, 松本 和幸, 石川 久, 津崎 龍一郎, 安中 哲也, 中司 敦子, 小池 和子, 三宅 康広, 白羽 英則, 和田 淳

    日本消化器病学会雑誌   109 ( 臨増総会 )   A325 - A325   2012年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • RUNX3の欠失はMRP発現を誘導しgemcitabine感受性に影響を与える

    堀口 繁, 白羽 英則, 永原 照也, 片岡 淳朗, 岩室 雅也, 高木 章乃夫, 能祖 一裕, 八木 孝仁, 山本 和秀

    日本消化器病学会雑誌   109 ( 臨増総会 )   A335 - A335   2012年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • HEPATIC ANGIOSARCOMA WITH CHARACTERISTIC LAPAROSCOPIC FINDINGS

    Tetsuya Yasunaka, Fusao Ikeda, Haruhiko Kobashi, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Hajime Hada, Kazuhide Yamamoto, Masayuki Nakano

    DIGESTIVE ENDOSCOPY   24 ( 2 )   124 - 124   2012年3月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1111/j.1443-1661.2011.01171.x

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  • Fulminant hepatitis: Who survives without liver transplantation?

    Yasuhiro Miyake, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    HEPATOLOGY RESEARCH   42 ( 1 )   60 - 67   2012年1月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Aim: In order to rescue more patients with fulminant hepatitis (FH) in a setting of the shortage of liver grafts, it is important not only to determine the suitable timing for liver transplantation (LT) but also to reduce avoidable operations for patients surviving without LT. This study aimed to identify prognostic parameters for survival without LT in FH patients.
    Methods: In 96 FH patients who did not receive LT, we examined prognostic parameters at the time of the diagnosis of FH, which were associated with patient's survival.
    Results: Fifty-three patients (55%) were female. The median age was 48 years. At the time of the diagnosis of FH, hepatic coma grade was II in 63 patients (66%), III in 22 (23%) and IV in 11 (11%). Forty-six patients (48%) were in a state of systemic inflammatory response syndrome (SIRS). Four parameters of age (&lt; 45 years), SIRS (no), direct bilirubin/total bilirubin ratio (&gt; 0.65), and total bilirubin (&lt; 12.0 mg/dL) were associated with patient's survival. Overall survival rate of eight patients ulfilling all four parameters were 88%. In 17 patients fulfilling any three parameters, 2-week, 4-week and overall survival rates were 82%, 77% and 71%, respectively. On the other hand, overall survival rate of 38 patients fulfilling any one parameter or none was less than 10%.
    Conclusions: Patients fulfilling all four parameters will be successfully treated without LT. In patients fulfilling any three parameters, intensive care including artificial liver support in expectation of hepatic regeneration during a few weeks may be possible.

    DOI: 10.1111/j.1872-034X.2011.00894.x

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  • 脂肪肝,脂肪性肝炎(NAFLD,NASH)

    山本和秀, 高木章乃夫

    MEDICINAL   2 ( 4 )   76 - 84   2012年

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  • SIRS Score Reflects Clinical Features of Non-Acetaminophen-Related Acute Liver Failure with Hepatic Coma

    Yasuhiro Miyake, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

    INTERNAL MEDICINE   51 ( 8 )   823 - 828   2012年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective In acetaminophen-induced acute liver failure (ALF), the hepatic coma grade worsens and mortality rates increase, as the number of systemic inflammatory response syndrome components fulfilled (SIRS score) increases. This study aimed to investigate the impact of SIRS score on clinical features of non-acetaminophen-related ALF.
    Methods Ninety-nine patients with non-acetaminophen-related ALF with hepatic coma who did not undergo liver transplantation were investigated. Each patient was given a SIRS score of 0, 1, 2, 3 or 4 at the time of diagnosis.
    Results At the diagnosis of ALF with hepatic coma, with the increase of SIRS score, hepatic coma grade and prothrombin activity were deteriorated. After the diagnosis of ALF with hepatic coma, 25 patients (25%) developed acute respiratory distress syndrome (ARDS), 31 patients (31%) developed disseminated intravascular coagulation (DIC), and 21 patients (22%) developed acute renal failure (ARF). Thirty-eight patients (38%) developed MOF. With the increase of SIRS score, frequencies of the development of ARDS, DIC and MOF increased. ARF was more frequently developed in patients with a SIRS score of 2 or higher. Overall, 36 patients (36%) survived. Overall survival rate was 66% in 29 patients with a score of 0, 43% in 21 patients with a score of 1, 17% in 29 patients with a score of 2 and 15% in 20 patients with a score of 3 or 4.
    Conclusion SIRS score will be useful for predicting not only the overall survival but also the development of complications such as ARDS, DIC and MOF in non-acetaminophen-related ALF with hepatic coma.

    DOI: 10.2169/internalmedicine.51.6686

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  • Serum Levels of Soluble Adhesion Molecules as Prognostic Factors for Acute Liver Failure

    Atsuyuki Ohnishi, Yasuhiro Miyake, Hiroshi Matsushita, Kazuyuki Matsumoto, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Kazuhiro Nouso, Kazuhide Yamamoto

    DIGESTION   86 ( 2 )   122 - 128   2012年

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    記述言語:英語   出版者・発行元:KARGER  

    Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF. Copyright (c) 2012 S. Karger AG, Basel

    DOI: 10.1159/000339496

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  • Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis.

    Kagawa H, Hiromasa T, Hara T, Takaki A, Yamanaka R, Sada KE, Makino H

    Clin Exp Nephrol   2012年

  • 核酸アナログ併用下、低用量HBIG・ワクチンによるB型肝炎ウイルスコントロール

    高木 章乃夫, 八木 孝仁, 貞森 裕, 松田 浩明, 安中 哲也, 篠浦 先, 楳田 祐三, 吉田 龍一, 内海 方嗣, 小池 和子, 池田 房雄, 三宅 康広, 白羽 英則, 保田 裕子, 藤原 俊義, 山本 和秀

    移植   46 ( 6 )   660 - 660   2011年12月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 移植後肝疾患における末梢血制御性T細胞の頻度の検討

    内海 方嗣, 小池 和子, 高木 章乃夫, 八木 孝仁, 渡辺 信和, Napier Stephanie C, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 吉田 龍一, 佐藤 太祐, 三宅 康広, 安中 哲也, 山本 和秀, 藤原 俊義

    移植   46 ( 6 )   678 - 678   2011年12月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 理想的な肝移植チームの在りかた 岡山大学病院における肝移植患者に対する全科横断的な取り組み アルコール性肝硬変患者に対する取り組みを中心に

    吉田 龍一, 八木 孝仁, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 佐藤 太佑, 内海 方嗣, 高木 章乃夫, 山本 和秀, 松本 洋輔, 河本 泰信, 保田 裕子, 清水 千聖, 藤原 俊義

    移植   46 ( 6 )   647 - 648   2011年12月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 血管新生関連サイトカインによる進行肝細胞癌の治療効果予測

    宮原 孝治, 能祖 一裕, 衣笠 秀明, 竹内 康人, 友田 健, 小林 沙代, 萩原 宏明, 安中 哲也, 桑木 健志, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 高木 章乃夫, 山本 和秀

    肝臓   52 ( Suppl.3 )   A810 - A810   2011年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌におけるPIVKA-II産生とEpithelial-Mesenchymal Transition

    白羽 英則, 松原 稔, 堀口 繁, 岩室 雅也, 片岡 淳朗, 永原 照也, 高木 章乃夫, 萩原 宏明, 桑木 健志, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    肝臓   52 ( Suppl.3 )   A839 - A839   2011年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • HCV特異的免疫応答およびIL28B遺伝子近傍SNPからみたC型肝炎による生体肝移植後の臨床経過についての検討

    津崎 龍一郎, 高木 章乃夫, 八木 孝仁, 池田 房雄, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 吉田 龍一, 内海 方嗣, 河合 大介, 安中 哲也, 小池 和子, 藤原 俊儀, 山本 和秀

    肝臓   52 ( Suppl.3 )   A858 - A858   2011年11月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • SERUM FOLLISTATIN AS A PROGNOSTIC MARKER FOR HEPATOCELLULAR CARCINOMA

    Kazuhiro Nouso, Takeshi Tomoda, Sayo Kobayashi, Koji Miyahara, Hiroaki Hagihara, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

    HEPATOLOGY   54   1375A - 1376A   2011年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • 劇症肝炎に対する肝移植の展望

    吉田 一博, 楳田 祐三, 貞森 裕, 松田 浩明, 篠浦 先, 吉田 龍一, 高木 章乃夫, 三宅 康広, 保田 裕子, 八木 孝仁, 藤原 俊義

    移植   46 ( 総会臨時 )   163 - 163   2011年10月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • THE RELATIONSHIPS OF PNPLA3 RS738409 POLYMORPHISM WITH THE ETIOLOGY OF LIVER DISEASES AND THE INCIDENCE OF HEPATOCELLULAR CARCINOMA

    Yasuto Takeuchi, Fusao Ikeda, Yuki Moritou, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Kazuhide Yamamoto

    HEPATOLOGY   54   1425A - 1425A   2011年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • 改正臓器移植法後の脳死肝移植登録の現状と問題点

    保田 裕子, 楳田 祐三, 清水 千聖, 高木 章乃夫, 八木 孝仁

    移植   46 ( 総会臨時 )   163 - 163   2011年10月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 先天性胆道閉鎖症に対する葛西手術後に肝細胞癌を発症した30歳台前半女性の一例

    太田 茂, 高木 章乃夫, 内海 方嗣, 松田 浩明, 大西 秀樹, 池田 房雄, 三宅 康広, 中村 進一郎, 白羽 英則, 岩崎 良章, 能祖 一裕, 八木 孝仁, 山本 和秀

    肝臓   52 ( Suppl.2 )   A614 - A614   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • NBI(Narrow Band Imaging)による腹腔鏡診断

    安中 哲也, 小橋 春彦, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    Gastroenterological Endoscopy   53 ( Suppl.2 )   2613 - 2613   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 肝細胞癌におけるepithelial-mesenchymal transition制御(The regulatory mechanism for epithelial-mesenchymal transition in hepatocellular carcinoma)

    白羽 英則, 仁科 慎一, 堀口 繁, 片岡 淳朗, 岩室 雅也, 松原 稔, 高岡 伸行, 高木 章乃夫, 大西 秀樹, 中村 進一郎, 能祖 一裕, 山本 和秀

    日本癌学会総会記事   70回   256 - 256   2011年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 本学関連病院における急性B型肝炎の実態調査

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 小橋 春彦, 藤岡 真一, 岡本 良一, 狩山 和也, 高山 裕基, 宮武 宏和, 守屋 昭男, 高口 浩一, 辰川 匡史, 金吉 俊彦, 坂田 達朗, 高畠 弘行, 守本 洋一, 山田 剛太郎, 山本 和秀

    肝臓   52 ( Suppl.2 )   A583 - A583   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝硬変に対するインターフェロン治療 血小板減少を伴うC型慢性肝炎・肝硬変症例へのインターフェロン治療に関するQOL評価の解析

    安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本門脈圧亢進症学会雑誌   17 ( 3 )   59 - 59   2011年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 生体肝移植後C型肝炎に対するオーダーメイド治療

    高木 章乃夫, 八木 孝仁, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 佐藤 太祐, 吉田 龍一, 三宅 康広, 山本 和秀

    日本門脈圧亢進症学会雑誌   17 ( 3 )   168 - 168   2011年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • Proteomic Analysis Reveals Aberrant Retinol Metabolism in Hepatitis C Virus Subgenomic Replicon-Harboring Cells

    Kazuko Koike, Akinobu Takaki, Nobuyuki Kato, Mamoru Ouchida, Tetsuya Yasunaka, Yasuhiro Miyake, Kazuhide Yamamoto

    GASTROENTEROLOGY   140 ( 5 )   S972 - S972   2011年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Hydrogen Rich Water Prevents Progression of NASH and Accompanying Hepatic Tumorigenesis in Mice

    Daisuke Kawai, Akinobu Takaki, Tetsuya Yasunaka, Kazuko Koike, Yasuhiro Miyake, Hidenori Shiraha, Kazuhide Yamamoto

    GASTROENTEROLOGY   140 ( 5 )   S703 - S703   2011年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 非アルコール性脂肪性肝炎(NASH)モデルマウスの病態進行に対する水素水の効果の検討

    河合 大介, 高木 章乃夫, 松本 和幸, 津崎 龍一郎, 安中 哲也, 中司 敦子, 小池 和子, 三宅 康広, 白羽 英則, 和田 淳, 山本 和秀

    肝臓   52 ( Suppl.1 )   A259 - A259   2011年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝再生医学研究の新展開 正常ヒト肝切除に伴う増殖因子の経時的変動 生体肝移植ドナーにおける検討

    松本 和幸, 三宅 康広, 楳田 祐三, 松田 浩明, 高木 章乃夫, 貞森 裕, 能祖 一裕, 八木 孝仁, 藤原 俊義, 山本 和秀

    肝臓   52 ( Suppl.1 )   A118 - A118   2011年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • LONG-TERM EFFICACY AND IMPACT ON HEPATOCELLULAR CARCINOMA DEVELOPMENT OF NUCLEOSIDE ANALOGUE TREATMENT WITH LAMIVUDINE AND ENTECAVIR FOR CHRONIC HEPATITIS B AND CIRRHOSIS

    H. Kobashi, Y. Miyake, F. Ikeda, T. Yasunaka, K. Nishino, A. Moriya, J. -I. Kubota, S. Nakamura, A. Takaki, K. Nouso, G. Yamada, K. Yamamoto

    JOURNAL OF HEPATOLOGY   54   S291 - S292   2011年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • 劇症肝炎患者の血清中における血管増殖因子レベルと予後

    高山 裕基, 三宅 康広, 能祖 一裕, 安中 哲也, 池田 房雄, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓   52 ( 3 )   220 - 220   2011年3月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 劇症肝炎患者の血清中における血管増殖因子レベルと予後

    高山 裕基, 三宅 康広, 能祖 一裕, 安中 哲也, 池田 房雄, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓   51 ( Suppl.2 )   A581 - A581   2010年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝癌においてカルボキシラーゼ活性は、EMTを制御する(Gamma-glutamyl-carboxylase regulates epithelial-mesenchymal transition in hepatocellular carcinoma)

    白羽 英則, 仁科 慎一, 松原 稔, 堀口 繁, 片岡 淳朗, 岩室 雅也, 高岡 伸行, 上村 雅之, 高木 章乃夫, 能祖 一裕, 山本 和秀

    日本癌学会総会記事   69回   120 - 120   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • DES-GAMMA-CARBOXY PROTHROMBIN AND ANGIOGENESIS IN HEPATOCELLULAR CARCINOMA

    H. Shiraha, S. Nishina, M. Matsubara, S. Horiguchi, M. Iwamuro, J. Kataoka, N. Takaoka, A. Takaki, K. Nouso, K. Yamamoto

    TUMOR BIOLOGY   31   S93 - S93   2010年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

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  • 高齢者肝疾患の治療適応と予後、何歳まで治療するべきか? 高齢者肝細胞癌の治療成績

    能祖 一裕, 小林 功幸, 中村 進一郎, 宮原 孝治, 友田 健, 小林 沙代, 高山 裕基, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本高齢消化器病学会誌   13 ( 1 )   89 - 89   2010年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本高齢消化器病学会  

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  • 慢性肝炎・肝硬変・肝細胞癌症例における末梢血酸化ストレス度・抗酸化ストレス度の検討

    高木 章乃夫, 玉木 直文, 小池 和子, 安中 哲也, 岩崎 良章, 池田 房雄, 三宅 康広, 白羽 英則, 小橋 春彦, 森田 学, 山本 和秀

    肝臓   51 ( Suppl.1 )   A181 - A181   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • AFP20ng/mL以下の肝細胞癌におけるL3分画測定の意義

    能祖 一裕, 小林 功幸, 中村 進一郎, 高山 裕基, 小林 沙代, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 小橋 春彦, 山本 和秀

    肝臓   51 ( Suppl.1 )   A203 - A203   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 自己免疫性肝疾患研究の進歩 CTLA4遺伝子の+49A/G多型は自己免疫性肝炎および原発性胆汁性肝硬変の疾患感受性に関連する

    三宅 康広, 安中 哲也, 池田 房雄, 中村 進一郎, 白羽 英則, 小林 功幸, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 小橋 春彦, 山本 和秀

    肝臓   51 ( Suppl.1 )   A58 - A58   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 消化器疾患と樹状細胞 病態の解明と治療法の開発 C型肝炎ウイルス(HCV)構成遺伝子導入およびHCVタンパク添加による樹状細胞機能の変化

    高木 章乃夫, 小池 和子, 安中 哲也, 三宅 康広, 白羽 英則, 岩崎 良章, 山本 和秀

    消化器と免疫   ( 46 )   59 - 63   2010年3月

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    記述言語:日本語   出版者・発行元:日本消化器免疫学会  

    【目的】HCV構成タンパクを健常者樹状細胞に添加した場合の、細胞表面マーカー・サイトカイン産生能の変化を検討した。【方法】健常成人末梢血よりCD14陽性細胞を回収。樹状細胞を樹立後、HCV構成タンパクを添加。細胞表面マーカーの発現を比較、また自己CD4陽性T細胞と、PPDを加えて抗原特異的リンパ球増殖能、および、Th1・Th2・Th17サイトカイン産生の測定を行った。【結果】CD86発現、IFNγ産生・IL17産生はNS4添加により低下したが、成熟刺激により回復した。【結論】HCV-NS4により樹状細胞のTh1産生能・Th17産生能が低下する。(著者抄録)

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  • 男性同性愛者のインターネット・コミュニティを介してGenotype AのB型急性肝炎と大腸アメーバ症を合併感染したと考えられる2症例

    小橋 春彦, 安中 哲也, 池田 房雄, 恩地 正浩, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 山本 和秀

    日本消化器病学会雑誌   107 ( 臨増総会 )   A405 - A405   2010年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 異常プロトロンビンの血管新生促進効果の検討

    白羽 英則, 松原 稔, 山本 和秀, 藤川 達也, 仁科 慎一, 堀口 繁, 上村 雅之, 高木 章乃夫, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 中村 進一郎, 小林 功幸, 能祖 一裕

    日本消化器病学会雑誌   107 ( 臨増総会 )   A265 - A265   2010年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 低用量HBIG・核酸アナログ併用によるHBV関連肝移植症例のHBV再発予防療法における血清HBcrAg、肝組織中HBV DNAの検討

    安中 哲也, 高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松田 浩明, 篠浦 先, 吉田 龍一, 内海 方嗣, 小池 和子, 河合 大介, 池田 房雄, 三宅 康広, 白羽 英則, 小橋 春彦, 山本 和秀

    肝臓   50 ( Suppl.3 )   A733 - A733   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 腹腔鏡でびまん性肝紫斑症の所見を呈した肝血管肉腫の1例

    安中 哲也, 小橋 春彦, 萩原 宏明, 桑木 健志, 歳森 淳一, 大西 秀樹, 池田 房雄, 三宅 康広, 白羽 英則, 中村 進一郎, 小林 功幸, 高木 章乃夫, 岩崎 良章, 能祖 一裕, 山本 和秀

    肝臓   50 ( Suppl.3 )   A764 - A764   2009年10月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • LOW-DOSE HEPATITIS B IMMUNOGLOBULIN AND NUCLEOS(T)IDE ANALOGUES THERAPY FOR POST-TRANSPLANTATION HEPATITIS B RESULTS IN LOW INTRAHEPATIC CCCDNA AND SERUM HBCRAG LEVELS

    Tetsuya Yasunaka, Akinobu Takaki, Takahito Yagi, Masashi Utsumi, Ryuichi Yoshida, Daisuke Sato, Fusao Ikeda, Yasuhiro Miyake, Susumu Shinoura, Hidenori Shiraha, Hiroaki Matsuda, Hiroshi Sadamori, Yoshiaki Iwasaki, Kazuhiro Nouso, Haruhiko Kobashi, Kazuhide Yamamoto

    HEPATOLOGY   50 ( 4 )   552A - 552A   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • 核酸アナログによりB型肝炎ウイルス関連肝細胞癌の予後は改善されている

    能祖 一裕, 小林 功幸, 中村 進一郎, 大西 秀樹, 歳森 淳一, 萩原 宏明, 桑木 健志, 安中 哲也, 池田 房雄, 三宅 康広, 白羽 英則, 高木 章乃夫, 岩崎 良章, 山本 和秀

    肝臓   50 ( Suppl.2 )   A560 - A560   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌における異常プロトロンビン血管新生亢進作用(Des-gamma-carboxy prothrombin promotes growth and angiogenesis in hepatocellular carcinoma)

    白羽 英則, 田中 盛富, 仁科 慎一, 松原 稔, 堀口 繁, 藤川 達也, 高岡 伸行, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事   68回   312 - 312   2009年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 当院における劇症肝炎肝移植症例の経過

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 佐藤 太祐, 吉田 龍一, 安中 哲也, 三宅 康広, 能祖 一裕, 小橋 春彦, 山本 和秀

    肝臓   50 ( 8 )   495 - 495   2009年8月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型慢性肝炎・肝硬変に対する核酸アナログ療法によるAFPの変化と肝細胞癌スクリーニングにおける診断的意義

    小橋 春彦, 安中 哲也, 池田 房雄, 三宅 康広, 谷口 英明, 白羽 英則, 中村 進一郎, 高木 章乃夫, 小林 功幸, 能祖 一裕, 岩崎 良章, 山本 和秀

    肝臓   50 ( Suppl.1 )   A193 - A193   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 血管新生因子としての異常プロトロンビン in vivoにおける検討

    白羽 英則, 藤川 達也, 仁科 慎一, 松原 稔, 田中 盛富, 高岡 伸行, 中西 豊, 上村 雅之, 上田 直樹, 高木 章乃夫, 山本 和秀

    肝臓   50 ( Suppl.1 )   A303 - A303   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 生体肝移植後C型肝炎症例におけるPD-L2発現の検討

    小池 和子, 高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松田 浩明, 安中 哲也, 三宅 康広, 池田 房雄, 白羽 英則, 小橋 春彦, 能祖 一裕, 山本 和秀

    肝臓   50 ( Suppl.1 )   A247 - A247   2009年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Matrix Metalloproteinase 3阻害による肝線維化抑制

    高岡 伸行, 上村 雅之, 松原 稔, 仁科 慎一, 藤川 達也, 田中 盛富, 中西 豊, 白羽 英則, 高木 章乃夫, 山本 和秀

    日本消化器病学会雑誌   106 ( 臨増総会 )   A368 - A368   2009年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 生体肝移植後C型肝炎に再発予防は必要か? インターフェロン無治療症例の検討

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 水野 憲司, 佐藤 太祐, 吉田 龍一, 庄司 凡, 小橋 春彦, 田中 紀章, 山本 和秀

    移植   44 ( 1 )   134 - 134   2009年2月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • 生体肝移植後B型肝炎再発予防としてのB型肝炎ウイルスワクチン効果

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 田中 紀章, 山本 和秀

    移植   44 ( 1 )   134 - 135   2009年2月

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    記述言語:日本語   出版者・発行元:(一社)日本移植学会  

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  • LOW-DOSE HEPATITIS B IMMUNOGLOBULIN WITH LAMIVUDINE FOR POST-TRANSPLANTATION HEPATITIS B VIRUS REACTIVATION AND MONTHLY HEPATITIS B VACCINE APPLICATION IS RELIABLE, COST-EFFECTIVE TREATMENT STRATEGIES

    Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hirsohi Sadamori, Yuzo Umeda, Susumu Shinoura, Hiroaki Matsuda, Tetsuya Yasunaka, Yasuhiro Miyake, Haruhiko Kobashi, Noriaki Tanaka, Kazuhide Yamamoto

    HEPATOLOGY   48 ( 4 )   586A - 586A   2008年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

    Web of Science

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  • RUNX3は肝細胞癌の進展を抑制する(RUNX3 regulates development of hepatocellular carcinoma)

    中西 豊, 白羽 英則, 田中 盛富, 仁科 慎一, 藤川 達也, 松尾 則行, 高岡 伸行, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事   67回   185 - 185   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • twist発現が肝細胞癌の転移・移動能を制御する(Twist expression regulates migration and invasion in hepatocellular carcinoma)

    白羽 英則, 松尾 則行, 田中 盛富, 藤川 達也, 高岡 伸行, 中西 豊, 仁科 慎一, 上村 雅之, 高木 章乃夫, 山本 和秀

    日本癌学会総会記事   67回   184 - 184   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 原因不明の急性肝不全に対し、生体肝移植を行った症例の検討

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 水野 憲司, 佐藤 太祐, 吉田 龍一, 庄司 凡, 小橋 春彦, 田中 紀章, 山本 和秀

    肝臓   49 ( 8 )   414 - 415   2008年8月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • C型肝硬変生体部分肝移植後のHCV特異的免疫応答の変化についての検討

    高木 章乃夫, 岩崎 良章, 八木 孝仁, 貞森 裕, 松田 浩明, 篠浦 先, 楳田 祐三, 吉田 龍一, 佐藤 太祐, 水野 憲司, 三宅 康広, 小池 和子, 小橋 春彦, 山本 和秀

    日本臨床免疫学会会誌   31 ( 4 )   299 - 299   2008年8月

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    記述言語:日本語   出版者・発行元:日本臨床免疫学会  

    DOI: 10.14906/jscisho.36.0.79.0

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  • A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis

    Tomohiro Nishida, Haruhiko Kobashi, Shin-Ichi Fujioka, Kozo Fujio, Kouichi Takaguchi, Hiroshi Ikeda, Mitsuhiko Kawaguchi, Masaharu Ando, Yasuyuki Araki, Toshihiro Higashi, Bon Shoji, Akinobu Takaki, Yoshiaki Iwasaki, Kohsaku Sakaguchi, Yasushi Shiratori, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   23 ( 5 )   794 - 803   2008年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Background and Aims: A prospective, non-randomized cohort study on long-term lamivudine treatment, comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus ( HBV)- related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease.
    Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV-DNA &gt; 5 log(10) copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis.
    Results: Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis.
    Conclusions: Lamivudine was effective in reducing HBV-DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.

    DOI: 10.1111/j.1440-1746.2007.05240.x

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  • B型肝炎ウイルスワクチンの今日的課題 生体肝移植後B型肝炎再発予防としてのB型肝炎ウイルスワクチンの位置づけ

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 庄司 凡, 安中 哲也, 小橋 春彦, 田中 紀章, 山本 和秀

    肝臓   49 ( Suppl.1 )   A76 - A76   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝硬変の成因別実態

    庄司 凡, 小橋 春彦, 安中 哲也, 萩 原, 桑木 健志, 歳森 淳一, 宮武 宏和, 白羽 英則, 中村 進一郎, 高木 章乃夫, 小林 功幸, 岩崎 良章, 山本 和秀

    肝臓   49 ( Suppl.1 )   A105 - A105   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • カルボキシラーゼ活性低下による肝癌進展

    白羽 英則, 高岡 伸行, 上田 直樹, 藤川 達也, 仁科 慎一, 中西 豊, 田中 盛富, 松尾 則行, 高木 章乃夫, 山本 和秀

    肝臓   49 ( Suppl.1 )   A241 - A241   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • A randomized trial of standard vs. dose-escalation dosing of ribavirin in combination therapy for chronic hepatitis c patients with genotype 1 and high viral load

    Yoshiaki Iwasaki, Yasuyuki Araki, Ryo-ichi Okamoto, Hideaki Taniguchi, Yasuhiro Makino, Tohru Ohnishi, Hiroyuki Shimomura, Minoru Tomita, Kazuhisa Yabushita, Yasushi Ishii, Masaharu Ando, Kumaki Hashimoto, Hiroshi Ikeda, Kouichi Takaguchi, Akinobu Takaki, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori, Kazuhide Yamamoto

    GASTROENTEROLOGY   134 ( 4 )   A788 - A789   2008年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • A 27-year-old man who died of acute liver failure probably due to trichloroethylene abuse

    Akinobu Takaki, Hideyuki Suzuki, Yoshiaki Iwasaki, Tomoko Takigawa, Keiki Ogino, Hiroaki Matsuda, Takahito Yagi, Motohiko Hanazaki, Hideki Nakatsuka, Hiroshi Katayama, Masaki Matsumi, Bon Shoji, Ryo Terada, Haruhiko Kobashi, Kohsaku Sakaguchi

    JOURNAL OF GASTROENTEROLOGY   43 ( 3 )   239 - 242   2008年3月

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    記述言語:英語   出版者・発行元:SPRINGER TOKYO  

    Acute liver failure from abuse of volatile substances is not usual. We encountered a case involving a 27-year-old man with acute liver and kidney failure followed by severe brain edema, probably caused by abuse of glue containing trichloroethylene. The clinical course was observed from the first day, when serum transaminases were normal, until death on day 12. The trichloroethylene metabolite trichloroacetate was detected in his urine.

    DOI: 10.1007/s00535-007-2146-5

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  • Lamivudine treatment improves the prognosis of fulminant hepatitis B

    Yasuhiro Miyake, Yoshiaki Iwasaki, Akinobu Takaki, Shin-ichi Fujioka, Kouichi Takaguchi, Hiroshi Ikeda, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    INTERNAL MEDICINE   47 ( 14 )   1293 - 1299   2008年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective The efficacy of lamivudine for fulminant hepatitis B has been reported in Europe and West Asia. However, in these reports, the main infection genotype is D. Furthermore, if lamivudine improves survival, prognostic factors for fulminant hepatitis B may differ from those reported previously. The aim of this study was to clarify the prognostic factors and the efficacy of lamivudine for fulminant hepatitis B in Japan, where the main infection genotype is B.
    Methods This study was a retrospective cohort study. We selected 37 consecutive patients with fulminant hepatitis due to acute hepatitis B virus infection. As 4 of them had received liver transplantation, the data of 33 patients with a median age of 45 (range, 20-74) years were analyzed.
    Results Lamivudine was administered to 10 patients. There were no differences in clinical features at the time of the diagnosis of fulminant hepatitis B between patients treated with and without lamivudine. Survival rates of patients treated with and without lamivudine were 70% and 26%, respectively. Age (&gt;= 45 years), systemic inflammatory response syndrome, and non-administration of lamivudine were associated with fatal outcomes. The survival rates of patients treated with and without lamivudine, who were in a state of systemic inflammatory response syndrome, were 50% and 9%, and in patients aged &gt;= 45 years, 50% and 8%, respectively.
    Conclusion This study suggests the efficacy of lamivudine for fulminant hepatitis B in the area where the main infection genotype is B. We consider that lamivudine is worth administering to patients with fulminant hepatitis B.

    DOI: 10.2169/internalmedicine.47.1061

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  • Gamma-Glutamyl-Carboxylase Regulates Development of Hepatocellular Carcinoma

    Hidenori Shiraha, Tatsuya Fujikawa, Naoki Ueda, Nobuyuki Takaoka, Yutaka Nakanishi, Shigetomi Tanaka, Shin-ichi Nishina, Akinobu Takaki, Kazuhide Yamamoto

    TUMOR BIOLOGY   29   41 - 41   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:KARGER  

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  • Hepatitis C virus could be eradicated with strong immune responses after withdrawing interferon treatment post living donor liver transplantation

    Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hiroshi Sadamori, Kazuko Koike, Masashi Tatsukawa, Haruhiko Kobashi, Kohsaku Sakaguchi

    HEPATOLOGY   46 ( 4 )   533A - 533A   2007年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • 30-P2-13 塩酸エピルビシンによる経カテーテル肝動脈内動注化学療法における副作用調査(副作用・有害事象,社会の期待に応える医療薬学を)

    駒橋 美妃, 松永 尚, 高木 章乃夫, 坂口 孝作, 千堂 年昭

    日本医療薬学会年会講演要旨集   17   2007年9月

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    記述言語:日本語   出版者・発行元:日本医療薬学会  

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  • Gamma-glutamyl carboxylase活性低下による肝細胞癌転移能の変化

    高岡 伸行, 白羽 英則, 藤川 達也, 上田 直樹, 中西 豊, 松尾 則行, 田中 盛富, 仁科 慎一, 高木 章乃夫, 坂口 孝作

    日本消化器病学会雑誌   104 ( 臨増大会 )   A679 - A679   2007年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • RUNX3による肝癌細胞株における細胞移動能の抑制(RUNX3 inhibits cell migration in hepatocellular carcinoma cell line)

    田中 盛富, 白羽 英則, 中西 豊, 上田 直樹, 高岡 伸行, 松尾 則行, 仁科 慎一, 藤川 達也, 上村 雅之, 高木 章乃夫, 坂口 孝作

    日本癌学会総会記事   66回   139 - 139   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 生体肝移植術前管理としての感染コントロールの重要性

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 成島 道樹, 庄司 凡, 寺田 亮, 小橋 春彦, 田中 紀章, 坂口 孝作

    肝臓   48 ( Suppl.1 )   A237 - A237   2007年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Des-gamma-carboxyl prothrombin-promoted vascular endothelial cell proliferation and migrations

    Tatsuya Fujikawa, Hidenori Shiraha, Naoki Ueda, Nobuyuki Takaoka, Yutaka Nakanishi, Noriyuki Matsuo, Shigetomi Tanaka, Shin-ichi Nishina, Mayumi Suzuki, Akinobu Takaki, Kohsaku Sakaguchi, Yasushi Shiratori

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 12 )   8741 - 8748   2007年3月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma. Previously, we have demonstrated that DCP stimulates cell proliferation in hepatocellular carcinoma cell lines through Met-Janus kinase 1 signal transducer and activator of transcription 3 signaling pathway. In the present study, we demonstrated that DCP induces both cell proliferation and migration in human umbilical vein endothelial cells. DCP was found to bind with the kinase insert domain receptor (KDR), alternatively referred to as vascular endothelial growth factor receptor-2. Furthermore, DCP induced autophosphorylation of KDR and its downstream effector phospholipase C-gamma and mitogen-activated protein kinase (MAPK). To support these results, we showed that DCP-induced cell proliferation and cell migration were inhibited by KDR short interfering RNA, KDR kinase inhibitor, or MAPK inhibitor. In conclusion, these results indicate that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities.

    DOI: 10.1074/jbc.M609358200

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  • A homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis

    Yasuhiro Miyake, Yoshiaki Iwasaki, Shin Ishikawa, Masashi Tatsukawa, Toru Nawa, Jun Kato, Akinobu Takaki, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    ACTA MEDICA OKAYAMA   61 ( 1 )   35 - 39   2007年2月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We report herein a case with acute hepatitis due to hepatitis B virus genotype Ale, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofiberscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required.

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  • Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation

    Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hiroshi Sadamori, Hiroyoshi Matsukawa, Hiroaki Matsuda, Susumu Shinoura, Yuuzou Umeda, Yasuhiro Miyake, Ryou Terada, Haruhiko Kobashi, Kohsaku Sakaguchi, Noriaki Tanaka, Yasushi Shiratori

    TRANSPLANTATION   83 ( 2 )   231 - 233   2007年1月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Hepatitis B immunoglobulin (HBIg) and lamivudine combination has been accepted as the best way to control hepatitis B recurrence after liver transplantation. However, the optimal dose of HBIg and the target titer of hepatitis B surface antibody (HBsAb) remain unclear. We report our satisfactory experience with high-dose HBIg in the early period followed by low-dose HBIg with lamivudine. Subjects comprised five patients with fulminant hepatitis (FH) and 18 patients with liver cirrhosis (LC) who underwent liver transplantation. HBIg at a dosage of 200 IU/kg per day was administered for one week postoperatively. Thereafter, HBIg was administered only for HBsAb titer &lt; 100 IU/L. After six months, HBIg was withdrawn in FH and administered in LC only for HBsAb titer &lt; 10 IU/L. Lamivudine was administered to two FH and all LC cases. Although two patients with LC showed transient hepatitis B surface antigen (HBsAg) recurrence, all patients remained HBsAg-negative at the final follow-up date. This method allows reliable and cost-effective control of hepatitis B recurrence.

    DOI: 10.1097/01.tp.0000246310.75638.86

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  • Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    Yuko Okamoto, Hirofumi Kawamoto, Akinobu Takaki, Etsuji Ishida, Tsuneyoshi Ogawa, Kenji Kuwaki, Yoshiyuki Kobayashi, Kohsaku Sakaguchi, Yasushi Shiratori

    EUROPEAN JOURNAL OF RADIOLOGY   61 ( 1 )   163 - 169   2007年1月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors.
    Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography.
    Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (K coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063).
    Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.ejrad.2006.08.014

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  • Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    Yuko Okamoto, Hirofumi Kawamoto, Akinobu Takaki, Etsuji Ishida, Tsuneyoshi Ogawa, Kenji Kuwaki, Yoshiyuki Kobayashi, Kohsaku Sakaguchi, Yasushi Shiratori

    EUROPEAN JOURNAL OF RADIOLOGY   61 ( 1 )   163 - 169   2007年1月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors.
    Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography.
    Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (K coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063).
    Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.ejrad.2006.08.014

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  • 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割

    白羽英則, 藤川達也, 上田直樹, 鈴木真由美, 高岡伸行, 高木章乃夫, 坂口孝作, 白鳥康史

    日本臨床検査自動化学会会誌   32 ( 2 )   164 - 165   2007年

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  • Clinical features of Japanese elderly patients with type 1 autoimmune hepatitis

    Yasuhiro Miyake, Yoshiaki Iwasaki, Akinobu Takaki, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    INTERNAL MEDICINE   46 ( 24 )   1945 - 1949   2007年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective In Caucasian type 1 autoimmune hepatitis patients with a main susceptibility of human leukocyte antigen DR3 and DR4, elderly patients have a higher frequency of concurrent autoimmune disease and cirrhosis at presentation. However, in Japanese patients, the disease is dominantly associated with DR4, and their clinical features may be different from those of previous reports. In this study, we assessed the clinical features of Japanese elderly patients with type 1 autoimmune hepatitis.
    Methods We investigated 160 consecutive patients with type 1 autoimmune hepatitis, consisting of 34 elderly patients (65 years) and 126 younger patients (&lt; 65 years).
    Results There were no differences in form of clinical onset, frequencies of concurrent autoimmune disease, positive proportions of anti-nuclear antibody and/or anti-smooth muscle antibody, and human leukocyte antigen DR status between the two groups. However, the elderly patients had lower serum levels of albumin (p= 0.0049), and higher frequencies of cirrhosis (F4) and pre-cirrhosis (F3) (p= 0.014) compared with the younger patients. In contrast, in elderly patients, the cumulative incidental rate of the normalization of serum alanine aminotransferase levels within 6 months after the introduction of initial treatment was higher in those treated with prednisolone &gt;= 20 mg/day than those treated only with ursodeoxycholic acid (p= 0.001).
    Conclusion We speculate that more years may pass between the occurrence of the disease and the presentation in Japanese elderly patients than in younger patients, and we considered that, even in elderly patients, those with advanced fibrosis should be treated with prednisolone in order to prevent progress of the disease into liver failure.

    DOI: 10.2169/internalmedicine.46.0420

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  • Combination of 5-FU and IFN alpha enhances IFN signaling pathway and caspase-8 activity, resulting in marked apoptosis in hepatoma cell lines

    Kazuko Koike, Akinobu Takaki, Masashi Tatsukawa, Mayumi Suzuki, Hidenori Shiraha, Yoshiaki Iwasaki, Kohsaku Sakaguchi, Yasushi Shiratori

    INTERNATIONAL JOURNAL OF ONCOLOGY   29 ( 5 )   1253 - 1261   2006年11月

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    記述言語:英語   出版者・発行元:PROFESSOR D A SPANDIDOS  

    Interferon (IFN) combined with 5-Fluorouracil (5-FU) treatment has recently been reported to show beneficial effects in patients with advanced hepatocellular carcinoma. IFNa is usually provided for this combination therapy. In this study, we investigated the molecular mechanisms of apoptosis induction in hepatoma cell lines with IFNa and 5-FU combination therapy from the view point of 5-FU's additive effect on interferon-related signaling pathways. Five hepatoma cell lines (Hep3B, Huh7, HLE, PLC/PRF/5, and HepG2) were tested for apoptosis inducibility by IFN alpha in the absence or presence of 5-FU. Hep3B was the most apoptosis sensitive to IFN plus 5-FU treatment. The JAK/STAT pathway transcriptional factor ISRE was activated more synergistically when 5-FU was added to IFN alpha treatments. Caspase-3, -9, and especially caspase-8 activity was higher with IFN a plus 5-FU than IFN or 5-FU alone. Inhibition of caspase-8, -9, c-Jun N-terminal kinase (INK), phosphatidylinositide 3-kinase (PI3K), and p38 mitogen-activated protein kinase (p38 MAPK) revealed that caspase-8 inhibition was the most effective at decreasing the apoptotic effects of IFN and/or 5-FU. In JAK1 and ISGF3y-silenced Hep3B cells, the apoptosis induction and caspase-8 activation levels by IFN, even in combination with 5-FU, were abrogated. In conclusion, caspase-8 is the most important factor that controls IFN and 5-FU-induced apoptosis in hepatoma cell lines.

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  • Endoscopic therapy for bleeding esophageal varices improves the outcome of Child C cirrhotic patients

    Shinichiro Hori, Akinobu Takaki, Hiroyuki Okada, Akiko Fujiwara, Ryuta Takenaka, Chiho Makidono, Yasushi Shiratori

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   21 ( 11 )   1704 - 1709   2006年11月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Background and Aims: Bleeding from esophageal varices is one of the frequent severe complications arising in patients with liver cirrhosis. The management of esophageal varices is therefore important for patient survival. The purpose of this study was to clarify the predictive factors for mortality in patients with Child C cirrhosis presenting with variceal bleeding.
    Methods: A retrospective analysis of 77 Child C cirrhotic patients with bleeding from esophageal varices was conducted. All patients received endoscopic therapy. Twenty-nine patients received endoscopic variceal ligation, and 48 patients received endoscopic injection sclerotherapy or endoscopic injection sclerotherapy with ligation. Univariate and multivariate analyses of clinical data were performed to identify the prognostic factors for survival for these 77 patients.
    Results: Fifty-seven of 77 patients received endoscopic therapy within 24 h after variceal bleeding, and bleeding was controlled in 55 (96.5%). The remaining 20 patients received endoscopic therapy more than 24 h after bleeding. Higher bilirubin level and rebleeding were the predictive parameters for 6-week survival in the 77 patients, according to univariate and multivariate analysis. Higher bilirubin level, refractory ascites, and the presence of hepatocellular carcinoma were the predictive parameters for mortality in 77 patients as determined by multivariate analysis.
    Conclusion: Endoscopic therapy was effective in controlling acute variceal bleeding of Child C cirrhotic patients. The prognosis of Child C stage patients presenting with variceal bleeding depended on the severity of liver damage and the presence of hepatocellular carcinoma.

    DOI: 10.1111/1440-1746.2006.04267.x

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  • Hepatitis C virus non-structural protein 4 downregulates differentiation and CD4 T cell stimulatory function of dendritic cells

    Akinobu Takaki, Yoshiaki Iwasaki, Kazuko Koike, Masashi Tatsukawa, Hidenori Shiraha, Kohsaku Sakaguchi, Eiichi Nakayama, Yasushi Shiratori

    HEPATOLOGY   44 ( 4 )   308A - 309A   2006年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • Gamma-glutamyl carboxylase inhibits cell migration in hepatocellular carcinoma cell lines

    Nobuyuki Takaoka, Hidenori Shiraha, Naoki Ueda, Shin-ichi Nishina, Tatsuya Fujikawa, Noriyuki Matsuo, Shigetomi Tanaka, Akinobu Takaki, Kohsaku Sakaguchi, Yasushi Shiratori

    HEPATOLOGY   44 ( 4 )   488A - 489A   2006年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • Gamma-glutamyl carboxylase活性低下による肝細胞癌悪性化

    高岡 伸行, 白羽 英則, 藤川 達也, 上田 直樹, 中西 豊, 松尾 則行, 田中 盛富, 仁科 慎一, 高木 章乃夫, 坂口 孝作, 白鳥 康史

    日本癌学会総会記事   65回   296 - 296   2006年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割

    白羽 英則, 藤川 達也, 上田 直樹, 鈴木 真由美, 高岡 伸行, 高木 章乃夫, 坂口 孝作, 白鳥 康史

    日本臨床検査自動化学会会誌   31 ( 4 )   352 - 352   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床検査自動化学会  

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  • B型慢性肝炎の血清中HBV-DNA全長塩基配列の検討 肝線維化の進展とゲノム変異

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 岩崎 良章, 小橋 春彦, 坂口 孝作, 白鳥 康史

    肝臓   47 ( Suppl.2 )   A391 - A391   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Early detection and quantification of lamivudine-resistant hepatitis B virus mutants by fluorescent biprobe hybridization assay in lamivudine-treated patients

    Fumi Umeoka, Yoshiaki Iwasaki, Masayuki Matsumura, Akinobu Takaki, Haruhiko Kobashi, Masashi Tatsukawa, Hidenori Shiraha, Shin-ichi Fujioka, Kohsaku Sakaguchi, Yasushi Shiratori

    JOURNAL OF GASTROENTEROLOGY   41 ( 7 )   693 - 701   2006年6月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    Background. Long-term lamivudine treatment induces the emergence of lamivudine-resistant hepatitis B virus (HBV). The objective of this study was to develop a fluorescent biprobe hybridization (FBH) assay for the detection and quantification of HBV mutants in the clinical course of lamivudine-treated patients and to evaluate its clinical usefulness. Methods. We developed an FBH assay to detect mutations in the HBV DNA polymerase gene. The assay's detection sensitivity was determined using a dilution series of wild-type/mutant plasmid DNA. Blood samples obtained from 27 lamivudine-treated patients were analyzed. Results. Mutant DNA levels as low as 10% of total HBV DNA were detected (sensitivity = 100%, specificity = 80%). HBV mutants were detected in five of the 27 patients during an average follow-up of 20 months after lamivudine administration. In one of the five patients, the YIDD mutant was detected at the initiation of lamivudine treatment, while the remaining four patients were identified as having YIDD mutants within 3 months after beginning lamivudine administration. Of the five patients with an HBV mutant, four developed breakthrough hepatitis more than 10 months after the detection of HBV mutants, following the reappearance or a re-increase of HBV DNA, characterized by a predominance of the mutant. The YIDD mutant was detected in one patient, even when the titer of the serum HBV DNA was below the detection limit of commercially available quantitative polymerase chain reaction. Conclusions. The FBH assay is an efficient method for detecting and quantifying HBV mutants, as early as 3 months after lamivudine administration.

    DOI: 10.1007/s00535-006-1834-x

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  • Addition of 5-FU enhances the IFN alpha induced signaling pathway and caspase-8 activities, resulting in marked apoptosis in hepatoma cell lines

    Kazuko Koike, Akinobu Takaki, Masashi Tatsukawa, Hidenori Shiraha, Yoshiaki Iwasaki, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori

    GASTROENTEROLOGY   130 ( 4 )   A832 - A832   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Short-term high-dose followed by long-term low-dose hepatitis B immune globulin and long-term lamivudine therapy prevented recurrent hepatitis B after living donor liver transplantation

    Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Hiroshi Sadamori, Hiroyoshi Matsukawa, Hiroaki Matsuda, Susumu Shinoura, Yuuzou Umeda, Haruhiko Kobashi, Kohsaku Sakaguchi, Noriaki Tanaka, Yasushi Shiratori

    GASTROENTEROLOGY   130 ( 4 )   A790 - A790   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 肝移植臨床の最前線 生体部分肝移植後のC型ウイルス肝炎の再燃・再発時におけるHCV特異的免疫応答変化の検討

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 小池 和子, 辰川 匡史, 白羽 英則, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 田中 紀章, 白鳥 康史

    肝臓   47 ( Suppl.1 )   A53 - A53   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型慢性肝炎 発癌例と非発癌例の血清中HBV-DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 小池 和子, 白羽 英則, 小橋 春彦, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓   47 ( Suppl.1 )   A150 - A150   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝移植臨床の最前線 B型肝炎ウイルス関連肝疾患における生体部分肝移植前後の抗ウイルス療法 ラミブジン併用低用量HBIG治療

    高木 章乃夫, 八木 孝仁, 岩崎 良章, 貞森 裕, 松川 啓義, 松田 浩明, 篠浦 先, 楳田 祐三, 小橋 春彦, 寺田 亮, 三宅 康広, 坂口 孝作, 田中 紀章, 白鳥 康史

    肝臓   47 ( Suppl.1 )   A52 - A52   2006年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Response to steroid therapy in patients with sclerosing cholangitis associated with elevated IgG4 level

    Ryo Terada, Hirofumi Kawamoto, Yasuhiro Miyake, Kohsaku Sakaguchi, Yoshiaki Iwasaki, Akinobu Takaki, Haruhiko Kobashi, Yoshiaki Kobayashi, Shin-Ichiro Nakamura, Kazuhide Yamamoto, Yasushi Shiratori

    GASTROENTEROLOGY   130 ( 4 )   A721 - A721   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Double mutation in core promoter region of hepatitis B virus genotype C is associated with an increased risk of hepatocellular carcinoma

    Masashi Tatsukawa, Akinobu Takaki, Kazuko Koike, Hidenori Shiraha, Haruhiko Kobashi, Yoshiaki Iwasaki, Yasushi Shiratori

    GASTROENTEROLOGY   130 ( 4 )   A751 - A751   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • Long-term monitoring of platelet count, as a non-invasive marker of hepatic fibrosis progression and/or regression in patients with chronic hepatitis C after interferon therapy

    H Taniguchi, Y Iwasaki, A Fujiwara, K Sakaguchi, A Moriya, PC Yu, A Takaki, SI Fujioka, H Shimornura, Y Shiratori

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   21 ( 1 )   281 - 287   2006年1月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Background: Platelet count has been shown to correlate with the hepatic fibrosis stage in chronic hepatitis C (CHC). The aim of the present study was to assess hepatic fibrosis progression or regression of CHC patients by long-term monitoring of the platelet count.
    Methods: A total of 429 interferon (IFN)-treated CHC patients were studied. Follow-up data on the platelet count were collected every 6 months after IFN therapy. The IFN response was defined as follows: complete responders (CR, n = 121) demonstrating persistent clearance of serum hepatitis C virus (HCV) RNA; biochemical responders (BR, n = 94) demonstrating alanine aminotransferase (ALT) normalization for &gt;= 6 months without eradication of HCV-RNA; and non-responder (NR, n = 214) demonstrating all other patterns.
    Results: In comparison with the baseline level, mean platelet count increased in the CR group from 0.5 years after IFN therapy (for each point, P &lt; 0.01), but significantly decreased in the NR group from I year after IFN therapy (for each point, P &lt; 0.01). In the BR group, an increase in mean platelet count was observed from 0.5 to 3.5 years following IFN therapy (for each point, P &lt; 0.01), followed by a gradual decrease.
    Conclusion: An increase from baseline values in platelet count was observed, regardless of the presence of HCV-RNA, in both the CR and BR groups, suggesting the importance of ALT normalization in preventing hepatic fibrosis progression in IFN-treated CHC patients. (C) 2006 Blackwell Publishing Asia Pty Ltd.

    DOI: 10.1111/j.1440-1746.2006.04201.x

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  • 目でみる診断学 Wilson病のKayser-Fleischerリング

    高木章乃夫, 白鳥康史

    成人病と生活習慣病院   36,4,350-351   2006年

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  • Novel splicing variant of the vitamin K-dependent gamma-glutamyl carboxylase (GGCX) causes des-gamma-carboxyl prothrombin production in human hepatocellular carcinoma cell lines

    N. Ueda, H. Shiraha, T. Fujikawa, M. Suzuki, N. Takanka, Y. Nakanishi, A. Takaki, Y. Shiratori

    JOURNAL OF HEPATOLOGY   44   S109 - S110   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • Des-gamma-carboxy prothrombin is an autologous growth factor for hepatocellular carcinoma

    H. Shiraha, M. Suzuki, T. Fujikawa, N. Ueda, N. Takaoka, Y. Nakanishi, A. Takaki, Y. Shiratori

    JOURNAL OF HEPATOLOGY   44   S117 - S117   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • Novel splicing variant of the vitamin K-dependent Fa-glutamyl carboxylase (GGCX) in human des-gamma-carboxyl prothrombin producing hepatocellular carcinoma cell lines

    N Ueda, H Shiraha, T Fujikawa, M Suzuki, N Takaoka, A Takaki, S Nakamura, Y Shiratori

    HEPATOLOGY   42 ( 4 )   528A - 528A   2005年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • C型肝炎ウイルス(HCV)構成遺伝子導入及びHCVタンパク貪食による樹状細胞(DC)表面マーカー及び機能の変化

    高木 章乃夫, 辰川 匡史, 小池 和子, 白羽 英則, 岩崎 良章, 白鳥 康史

    肝臓   46 ( Suppl.1 )   A225 - A225   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌における異常プロトロンビンの増殖制御機構

    白羽 英則, 鈴木 真由美, 藤川 達也, 高岡 伸行, 上田 直樹, 高木 章乃夫, 白鳥 康史

    肝臓   46 ( Suppl.1 )   A141 - A141   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • B型慢性肝炎発癌例と非発癌例の血清中HBV-DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 藤岡 真一, 岩崎 良章, 白鳥 康史

    肝臓   46 ( Suppl.1 )   A190 - A190   2005年5月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma

    M Suzuki, H Shiraha, T Fujikawa, N Takaoka, N Ueda, Y Nakanishi, K Koike, A Takaki, Y Shiratori

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 8 )   6409 - 6415   2005年2月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.

    DOI: 10.1074/jbc.M406714200

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  • 肝臓 C型肝炎 ウイルス,病態,診断

    高木章乃夫, 白鳥康史

    Annual Review消化器2005巻   259-262   2005年

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  • 【利尿薬の正しい使い方 基礎と臨床】 肝疾患と腹水

    高木章乃夫, 白鳥康史

    腎と透析   58,2,146-149   2005年

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  • 【ウイルス肝炎と肝移植】 施設における現状と対策 内科医より 岡山大学病院において

    高木章乃夫, 八木孝仁, 岩崎良章, 坂口孝作, 白鳥康史

    今日の移植   18,2,213-215   2005年

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  • 【年齢・性差と肝胆膵疾患】 年齢・性差と各種肝疾患 C型肝障害

    平岡佐規子, 高木章乃夫, 白鳥康史

    肝・胆・膵   51,2,199-204   2005年

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  • Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma.

    T Fujikawa, M Suzuki, H Shiraha, N Takaoka, N Ueda, Y Nakanishi, K Koike, A Takaki, Y Shiratori

    HEPATOLOGY   40 ( 4 )   602A - 603A   2004年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • B型慢性肝炎 発癌例と非発癌例の血清中HBV DNA全長塩基配列の相違

    辰川 匡史, 高木 章乃夫, 白羽 英則, 小池 和子, 藤岡 真一, 岩崎 良章, 白鳥 康史

    肝臓   45 ( Suppl.2 )   A451 - A451   2004年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • インターフェロンα8はα2よりもcaspaseを強く活性化し,抗癌剤による肝細胞癌株アポトーシスを誘導する

    小池 和子, 高木 章乃夫, 辰川 匡史, 白羽 英則, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓   45 ( Suppl.2 )   A484 - A484   2004年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌におけるRUNX3の発現とその機能解析

    中西 豊, 白羽 英則, 上田 直樹, 藤川 達也, 鈴木 真由美, 高岡 伸行, 高木 章乃夫, 白鳥 康史

    日本消化器病学会雑誌   101 ( 臨増大会 )   A811 - A811   2004年9月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 病気と薬の説明ガイド2004-消化器疾患 肝炎

    高木章乃夫, 小池和子, 白鳥康史

    薬局   55:999-1005   2004年

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  • 急性肝不全の概念と分類の見直し-劇症肝炎に対する肝移植適応ガイドラインの問題点について

    三宅康弘, 三好健司, 岡本良一, 森井和彦, 藤尾耕三, 大本昌樹, 池田弘, 小橋春彦, 牧野泰裕, 坂井宣之, 高口浩一, 荒木康之, 安東正晴, 喜田恵治, 高木章乃夫, 岩崎良章, 坂口孝作, 白鳥康史

    消化器科   38(1)   2004年

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  • 消化器疾患と免疫-基礎-肝臓の免疫装置と免疫担当細胞

    高木章乃夫, 小池和子, 白鳥康史

    消化器科   35(11)   2004年

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  • 肝炎の臨床よりの問題 臨床的諸問題の展開と今後の展望

    高木章乃夫, 岩崎良章, 白鳥康史

    肝疾患Review 2004   25-38   2004年

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  • 肝炎の臨床よりの問題-臨床的諸問題の展開と今後の展望

    高木章乃夫, 岩崎良章, 白鳥康史

    肝疾患Review   25-38   2004年

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  • 肝炎の自然史-C型肝炎

    高木章乃夫, 小池和子, 辰川匡史, 岩崎良章, 白鳥康史

    臨床と研究   81,8,1233-1236   2004年

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  • 肝炎の自然史-C型肝炎

    高木章乃夫, 小池和子, 辰川匡史, 岩崎良章, 白鳥康史

    臨床と研究   81(8)   2004年

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  • HCV感染に対する宿主の免疫学的監視機構のメカニズム

    高木章乃夫, 小池和子, 白鳥康史

    日本臨床 ウィルス性肝炎(上)-基礎・臨床研究の進歩-   62,7,143-146   2004年

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  • ウイルス肝炎 新たな治療法-ウイルス肝炎の自然経過と治療指針-C型慢性肝炎の自然経過と治療方針

    高木章乃夫, 小池和子, 岩崎良章, 白鳥康史

    内科   93(3)、425-429   2004年

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  • C型肝炎治療の実際と展望

    白鳥康史, 岩崎良章, 小林功幸, 高木章乃夫, 坂口孝作

    日本医事新報   4145,1-16   2004年

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  • HBV感染に対する宿主の免疫学的監視機構と感染成立機序

    高木章乃夫, 辰川匡史, 小池和子, 白鳥康史

    日本臨床   62(8)   2004年

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  • B型肝炎ウイルス関連検査法 HBV Subtype決定法-分類とタイピングの実際

    高木章乃夫, 辰川匡史, 白鳥康史

    日本臨床   62(8)、149-152   2004年

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  • C型肝炎ウイルス(HCV)の分子免疫学 HCV感染時の免疫応答の程度とMHCClassIIの多型性との関連

    小池和子, 高木章乃夫, 白鳥康史

    日本臨床   62(7)   2004年

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  • Ⅱ.B型肝炎ウィルス(HBV)B型ウィルス肝炎の分子免疫学 HBV感染と免疫機序 HBV感染に対する宿主の免疫学的監視機構と感染成立機序

    高木章乃夫, 辰川匡史, 小池和子, 白鳥康史

    日本臨床 ウィルス性肝炎(下)-基礎・臨床研究の進歩-   62,8,62-65   2004年

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  • Ⅱ.B型肝炎ウィルス(HBV)関連検査法 HBV subtype決定法 -分類とtypingの実際-

    高木章乃夫, 辰川匡史, 白鳥康史

    日本臨床 ウィルス性肝炎(下)-基礎・臨床研究の進歩-   62,8,149-152   2004年

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  • 【プライマリケア医のための肝臓疾患診療マニュアル】わが国におけるウィルス性慢性肝炎診療の現状と展望

    三宅康広, 高木章乃夫, 白鳥康史

    治療   86,9,2435-2440   2004年

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  • 【病気と薬の説明ガイド2004】 消化器疾患 肝炎

    高木章乃夫, 小池和子, 白鳥康史

    薬局   55,999-1005   2004年

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  • 【急性肝不全の概念と分類の見直し】「劇症肝炎に対する肝移植適応ガイドライン」の問題点について

    三宅康広, 三好健司, 岡本良一, 森井和彦, 藤尾耕三, 大本昌樹, 池田弘, 小橋春彦, 牧野泰裕, 坂井宣之, 高口浩一, 荒木康之, 安東正晴, 喜田恵治, 高木章乃夫, 岩崎良章, 坂口孝作, 白鳥康史

    消化器科   2004年

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  • 【ウィルス肝炎 新たな治療法】ウィルス肝炎の自然経過と治療指針 C型慢性肝炎の自然経過と治療方針

    高木章乃夫, 小池和子, 岩崎良章, 白鳥康史

    内科   93,3,425-429   2004年

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  • 高マグネシウム血症により意識障害を来たした慢性腎不全の2例

    中司敦子, 神崎資子, 高木章乃夫, 岩田康義, 福島正樹, 池田弘

    日本透析医学会雑誌   2004年

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  • Ⅰ.C型肝炎ウィルス(HCV) C型ウィルス肝炎の分子免疫学 体液性免疫 HCV感染時の免疫応答の程度とMHC classⅡの多型性との関連

    小池和子, 高木章乃夫, 白鳥康史

    日本臨床 ウィルス性肝炎(上)-基礎・臨床研究の進歩-   62,7,147-150   2004年

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  • Effects of pulsing procedure of interleukin-12 in combination with interleukin-2 on the activation of peripheral blood lymphocytes derived from patients with hepatocellular carcinoma

    T Sawayama, K Sakaguchi, T Senoh, T Ohta, M Nishimura, A Takaki, T Tsuji, Y Shiratori

    ACTA MEDICA OKAYAMA   57 ( 6 )   285 - 292   2003年12月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell activity decreases significantly, and the reduced activity may be associated with the progression of HCC. In this study we evaluated the effects of pulsing with interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the presence of IL-2 and/or IL-12. After 24h of incubation, the levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha presented in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-gamma and TNF-alpha production of PBL pulsed by a combination of IL-2 and IL-12 was significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone. The mRNA encoding perforin, granzyme B, as well as IFN-gamma and TNF-alpha, were markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of IFN-gamma and TNF-alpha, and the expression of perforin and granzyme B mRNA in PBL obtained from HCC patients, as well as in those obtained from normal subjects. These results indicate that adoptive immunotherapy based on PBL pulsed with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for HCC treatment.

    DOI: 10.18926/AMO/32813

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  • インターフェロンαサブタイプによる肝癌細胞株アポトーシス誘導効果の相違

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 坂口 孝作, 稲葉 二朗, 窪田 規一, 白鳥 康史

    日本免疫学会総会・学術集会記録   33   331 - 331   2003年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本免疫学会  

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  • Interferon alpha 8 and 2 show differential activation of apoptosis pathway and growth factor pathway in human hepatoma cell lines.

    A Takaki, K Koike, H Shiraha, Y Iwasaki, K Sakaguchi, N Inaba, K Kubota, Y Shiratori

    HEPATOLOGY   38 ( 4 )   406A - 406A   2003年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO  

    Web of Science

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  • C型肝炎ウイルス構成遺伝子導入による樹状細胞HLA及びCostimulatory molecule発現の変化についての検討

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 中山 睿一, 白鳥 康史

    肝臓   44 ( Suppl.2 )   A433 - A433   2003年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Des-gamma-carboxy prothrombin is an autocrine mitogen for hepatocellular carcinoma

    M Suzuki, H Shiraha, T Fujikawa, N Takaoka, A Takaki, Y Nakanishi, N Ueda, K Koike, K Sakaguchi, Y Shiratori

    GASTROENTEROLOGY   124 ( 4 )   A285 - A285   2003年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO  

    Web of Science

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  • インターフェロンαサブタイプによる肝癌細胞アポトーシス誘導能の相違と,細胞内情報伝達系及びアポトーシス関連遺伝子の変化の関連

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 坂口 孝作, 白鳥 康史

    肝臓   44 ( Suppl.1 )   A168 - A168   2003年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • インターフェロンαサブタイプによる肝癌細胞アポトーシス誘導能の相違 インターフェロンα2とα8で異なる細胞内情報伝達系とアポトーシス関連遺伝子の連係

    高木 章乃夫, 小池 和子, 白羽 英則, 岩崎 良章, 白鳥 康史

    日本消化器病学会雑誌   100 ( 臨増総会 )   A150 - A150   2003年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • C型肝炎治療の実際と展望

    白鳥康史, 医歯学総合研究科, 消化器肝臓感染症内科学, 岩崎良章, 小林功幸, 高木章乃夫, 坂口孝作

    日本医事新報   1-10   2003年

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  • 【消化器疾患と免疫】 基礎 肝臓の免疫装置と免疫担当細胞

    高木章乃夫, 医歯学総合研究科, 消化器肝臓感染症内科, 小池和子, 白鳥康史

    現代医療   35,11,2504-2508   2003年

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  • 【内科キーワード2003】 肝・胆・膵 インターフェロン治療と肝線維化緩解

    坂口孝作, 消化器肝臓感染症内科, 高木章乃夫, 河本博文, 白鳥康史

    内科   91,6,1074   2003年

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  • 約25年の経過で肝硬変に進展した体質性黄疸の一例

    藤田英行, 医学部, 学科, 藤岡真一, 寺田亮, 馬場伸介, 中西豊, 朴成郁, 高木章乃夫, 岩崎良章, 山本和秀, 白鳥康史

    日本消化器内視鏡学会雑誌   2003年

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  • 【ウイルス肝炎診療update】 HCVの構造と研究の進歩 HCVと免疫

    高木章乃夫, 消化器肝臓感染症内科学, 小池和子, 白鳥康史

    臨床医   29,5,633-635   2003年

     詳細を見る

  • 糖尿病性腎症に合併したANCA関連急速進行性糸球体腎炎の1例

    中司敦子, 佐藤千景, 岩田康義, 高木章乃夫, 福島正樹, 津嘉山朝達, 西崎哲一

    腎と透析   2002年

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  • 【肝炎 EBMに基づく最新の知見と最新の治療】 ウイルス肝炎における肝線維化とその臨床的意義

    高木章乃夫, 医歯総合研究, 消化器肝臓感染症内科, 白鳥康史

    Medical Practice   19,6,973-975   2002年

     詳細を見る

  • ANCA関連腎炎の治療と予後に関する検討

    中司敦子, 高木章乃夫, 岩田康義, 福島正樹

    倉敷中央病院年報   2002年

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  • アンギオテンシン変換酵素阻害剤(ACE-I)投与中に発生した急性腎不全症例の検討

    高木章乃夫, 岩田康義, 佐藤千景, 江口潤, 中司敦子, 福島正樹

    ICUとCCU   2002年

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  • 慢性B型肝炎に巣状分節性糸球体硬化症(FSGS)によるネフローゼ症候群を合併し,ステロイド,LDL吸着療法にて緩解した1例

    高木章乃夫, 央病院, 腎臓内科, 中司敦子, 佐藤千景, 岩田康義, 池田弘, 福島正樹

    日本腎臓学会誌   2002年

  • Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C

    Akinobu Takaki, Manfred Wiese, Geert Maertens, Erik Depla, Ulrike Seifert, Anke Liebetrau, Jeffery L. Miller, Michael P. Manns, Barbara Rehermann

    Nature Medicine   6 ( 5 )   578 - 582   2000年5月

     詳細を見る

    記述言語:英語  

    As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV- infected cells and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-γ-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4+ and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

    DOI: 10.1038/75063

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  • Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C

    Akinobu Takaki, Manfred Wiese, Geert Maertens, Erik Depla, Ulrike Seifert, Anke Liebetrau, Jeffery L. Miller, Michael P. Manns, Barbara Rehermann

    Nature Medicine   6 ( 5 )   578 - 582   2000年5月

     詳細を見る

    記述言語:英語  

    As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV- infected cells and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-γ-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4+ and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

    DOI: 10.1038/75063

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  • Increase in CD95 (Fas/APO-1)-positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

    Shin Ogawa, Kohsaku Sakaguchi, Akinobu Takaki, Kunihiro Shiraga, Tomoyuki Sawayama, Hirokazu Mouri, Manabi Miyashita, Norio Koide, Takao Tsuji

    Journal of Gastroenterology and Hepatology (Australia)   15 ( 1 )   69 - 75   2000年

     詳細を見る

    記述言語:英語   出版者・発行元:Blackwell Publishing  

    Background: The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). Methods: The CD95 and Bcl-2 expressions within CD4+ T, CD8+ T, and CD19+ B cell subsets were analysed by two-colour flow cytometry. Results: The surface expression of CD95 was significantly high in both the CD4+ T and CD8+ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO- to primed CD45RO+ CD4+T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl2- positive cells in the CD4+T cell, CD8+T cell and CD19+ B cell subsets among the patient groups and normal subjects. Conclusions: These results indicate that an increase in CD4+T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non- specific activation oft lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI). (C) 2000 Blackwell Science Asia Pty Ltd.

    DOI: 10.1046/j.1440-1746.2000.02044.x

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  • Increase in CD95 (Fas/APO-1)-positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

    Shin Ogawa, Kohsaku Sakaguchi, Akinobu Takaki, Kunihiro Shiraga, Tomoyuki Sawayama, Hirokazu Mouri, Manabi Miyashita, Norio Koide, Takao Tsuji

    Journal of Gastroenterology and Hepatology (Australia)   15 ( 1 )   69 - 75   2000年

     詳細を見る

    記述言語:英語   出版者・発行元:Blackwell Publishing  

    Background: The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). Methods: The CD95 and Bcl-2 expressions within CD4+ T, CD8+ T, and CD19+ B cell subsets were analysed by two-colour flow cytometry. Results: The surface expression of CD95 was significantly high in both the CD4+ T and CD8+ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO- to primed CD45RO+ CD4+T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl2- positive cells in the CD4+T cell, CD8+T cell and CD19+ B cell subsets among the patient groups and normal subjects. Conclusions: These results indicate that an increase in CD4+T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non- specific activation oft lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI). (C) 2000 Blackwell Science Asia Pty Ltd.

    DOI: 10.1046/j.1440-1746.2000.02044.x

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▼全件表示

講演・口頭発表等

  • NASH肝癌モデルに対する整腸剤ベルベリンの有用性と腸内環境変化の重要性

    第25回 日本肝臓学会大会 神戸 2021年 

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    開催年月日: 2021年11月4日 - 2021年11月7日

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  • 移行期医療におけるFontan関連肝疾患(FALD)診療の現状と問題

    第57回 日本肝臓学会総会 札幌 2021年 

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    開催年月日: 2021年6月17日 - 2021年6月18日

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  • ベルベリンのNASH肝癌モデル腸内環境に対する介入効果

    第107回 日本消化器病学会総会 東京 2021年 

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    開催年月日: 2021年4月15日 - 2021年4月17日

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  • 肝癌に対する脳死肝移植適応基準の拡大による実地診療への寄与

    第38回 日本肝移植学会学術総会 松山 2020年 

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    開催年月日: 2020年12月25日 - 2020年12月26日

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  • Milan 基準超5-5-500内肝細胞癌に対する肝移植後経過の実態

    第56回 日本肝臓学会総会 大阪 2020年 

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    開催年月日: 2020年8月28日 - 2020年8月29日

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  • 整腸剤ベルベリンのNASH肝癌モデルでの効果

    第56回 日本肝臓学会総会 大阪 2020年 

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    開催年月日: 2020年8月28日 - 2020年8月29日

    会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • NASH肝癌モデルでのベルベリンの有用性

    第57回 日本消化器免疫学会総会 

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    開催年月日: 2020年7月3日 - 2020年7月4日

    会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • The effect of short and long term administration of L-carnitine on liver cirrhosis patients

    APASL STC 2016  2016年 

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  • 膵癌予後不良例における酸化ストレス亢進状態の重要性

    JDDW2016  2016年 

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  • 肝移植1年後生存に関与する術前リスクとしての潜在的門脈肺高血圧症の重要性

    第23回日本門脈圧亢進症学会総会  2016年 

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  • 溶血発作を伴う肝不全を呈したが肝移植を回避できたWilson病の1 例

    第106回日本消化器病学会中国支部例会  2016年 

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  • Oxidative Stress Controlling Agents Are Effective for NSAIDs-Induced Small Intestinal Injuries

    DDW2016  2016年 

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  • 高アンモニア血症を有する肝硬変患者に対するL-カルニチン製剤の有用性規定因子と長期投与関連因子の検討

    第52回日本肝臓学会総会  2016年 

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  • Budd-Chiari症候群に伴う門脈圧亢進症に対し、肝静脈拡張術が奏効した1例

    第5回中国門脈圧亢進症研究会  2016年 

     詳細を見る

  • Serum IP-10 Is a Highly Sensitive Marker for Discriminating Non-Alcoholic Fatty Liver and Non-Alcoholic Steatohepatitis

    DDW2016  2016年 

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  • NSAIDs長期内服者における酸化ストレス状態とカプセル内視鏡所見についての検討

    第91回日本消化器内視鏡学会総会  2016年 

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  • NSAIDs起因性小腸粘膜障害における抗酸化治療の可能性

    第102回日本消化器病学会総会  2016年 

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  • インスリン抵抗性とTLR2刺激の非アルコール性脂肪性肝炎病態への関与

    第102回日本消化器病学会総会  2016年 

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  • 当施設における肝移植の現状

    第51回日本肝臓学会総会  2015年 

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  • ウスモデルを用いたNSAIDs起因性小腸粘膜障害に対する抗酸化 治療の有効性に関する検討

    第101回日本消化器病学会総会  2015年 

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  • 肝移植後の肥満と腎機能経過

    第101回日本消化器病学会総会  2015年 

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  • Oxidative stress balance is dysregulated in cholangiocarcinoma that could be improved with L-carnitine administration

    Digestive Disease Week 2015  2015年 

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  • 肝移植後C型肝炎の特殊性:免疫制御機構に及ぼす免疫抑制剤と キメリズムの影響

    第101回日本消化器病学会総会  2015年 

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  • 門脈圧亢進症における心肺機能と酸化ストレス

    第101回日本消化器病学会総会  2015年 

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  • 代償期および非代償期肝硬変での潜在的肝肺症候群・肺高血圧の臨床的特徴

    第19回日本肝臓学会大会  2015年 

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  • 急性肝不全の脳死登録から生体肝移植への切り替え症例の検討

    第51回日本移植学会総会  2015年 

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  • 胆管癌における酸化ストレスと便中胆汁酸の関連性の検討

    第19回日本肝臓学会大会  2015年 

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  • 胆管癌における酸化ストレスの関与と糖尿病関連肝内胆管細胞癌モデルにおける抗酸化治療の有用性

    第51回日本肝臓学会総会  2015年 

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  • Entecavir Reduces Hepatocarcinogenesis in Patients With Chronic Hepatitis B

    Digestive Disease Week 2015  2015年 

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  • 門脈圧亢進症における心肺機能と酸化ストレスについての検討

    第22回日本門脈圧亢進症学会  2015年 

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  • 当院に紹介された急性肝不全の推移

    第40回日本急性肝不全研究会  2014年 

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  • Entecavir reduces the incidence of hepatocellular carcinoma in patients with chronic hepatitis B.

    AASLD The Liver Meeting 2014  2014年 

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  • L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway

    AASLD The Liver Meeting 2014  2014年 

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  • 急性肝不全治療においてコーディネータが難渋する点

    第40回日本急性肝不全研究会  2014年 

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  • Unique profile of liver perfusate mononuclear cells transferable to liver transplantation recipients

    United European Gastroenterology Week 2014,  2014年 

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    第50回日本肝臓学会総会  2014年 

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    第99回日本消化器病学会総会  2013年 

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    第99回日本消化器病学会総会  2013年 

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    ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASE 2013  2013年 

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    ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASE 2013  2013年 

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    第40回日本肝臓学会西部会  2013年 

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    ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASE 2013  2013年 

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  • Frequency of regulatory T cell and HCV antigen specific immune response in recurrent hepatitis C after a liver transplantation.

    UEGW2013  2013年 

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  • Frequency of regulatory T cell and HCV antigen specific immune response in recurrent hepatitis C after liver transplantation.

    ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASE 2013  2013年 

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  • Strong hepatitis C virus-specific T-cell immune responses correlate with lower hepatitis activities and donor IL28B major genotype in the early period after living donor liver transplantation.

    ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASE 2013  2013年 

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  • 脳死肝移植登録患者の経過-劇症肝炎10点以前と以後

    第99回日本消化器病学会総会  2013年 

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  • RUNX3の欠失はMRP発現を誘導しgemcitabine感受性に影響を与える

    第98回日本消化器病学会総会  2012年 

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  • C型慢性肝炎2型高ウイルス量症例に対するペグインターフェロンα+リバビリン併用療法の期間延長による治療効果改善の検討

    第48回日本肝臓学会総会  2012年 

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  • 腹腔鏡検査での赤色紋理は、B型慢性肝炎の肝発癌危険因子である

    第48回日本肝臓学会総会  2012年 

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  • 貧血を契機に発見され肝硬変に至っていた小児自己免疫性肝炎の一例

    第107回 日本内科学会中国地方会  2012年 

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  • C型慢性肝炎に対するペグインターフェロンα+リバビリン併用療法における血清フェリチン値の検討

    第48回日本肝臓学会総会  2012年 

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  • 移植後B型肝炎に対するHBVワクチンは非血縁・HBs抗体高値ドナーで有用である

    第48回日本肝臓学会総会  2012年 

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  • 自己免疫性肝炎の新規診断補助マーカーとしての抗PD‐1抗体及び抗BTLA抗体

    第48回日本肝臓学会総会  2012年 

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    第48回日本肝臓学会総会  2012年 

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    第48回日本肝臓学会総会  2012年