Faculty Profiles - ONISHI Hideki

Papers - ONISHI Hideki

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Response to the letter: "Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab". Reviewed International journal

Tatsuya Kikuchi, Yasuto Takeuchi, Kazuhiro Nouso, Kazuya Kariyama, Kenji Kuwaki, Junichi Toshimori, Shota Iwado, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Toshifumi Tada, Tetsuya Yasunaka, Masahiro Sakata, Masahiko Sue, Nozomi Miyake, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Motoyuki Otsuka

Liver international : official journal of the International Association for the Study of the Liver 44 ( 7 ) 1736 - 1737 2024.7

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab. Reviewed International journal

Tatsuya Kikuchi, Yasuto Takeuchi, Kazuhiro Nouso, Kazuya Kariyama, Kenji Kuwaki, Junichi Toshimori, Shota Iwado, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Toshifumi Tada, Tetsuya Yasunaka, Masahiro Sakata, Masahiko Sue, Nozomi Miyake, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Motoyuki Otsuka

Liver international : official journal of the International Association for the Study of the Liver 44 ( 6 ) 1456 - 1463 2024.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

DOI： 10.1111/liv.15907

Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis. Reviewed

Masahiro Takahara, Sakiko Hiraoka, Masayasu Ohmori, Keiko Takeuchi, Kensuke Takei, Yuki Aoyama, Eriko Yasutomi, Shoko Igawa, Toshihiro Inokuchi, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Keita Harada, Hideki Onishi, Hiroyuki Okada

Acta medica Okayama 78 ( 1 ) 79 - 83 2024.2

Language：English Publishing type：Research paper (scientific journal)

This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies.

DOI： 10.18926/AMO/66674

Anti-PD-1 Autoantibody Predicts Survival of Patients With Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

Yuki Sasaki, Kazuyuki Matsumoto, Akinobu Takaki, Takuya Adachi, Masahiro Takahara, Keita Ozato, Yasuto Takeuchi, Masahiko Sue, Nozomi Miyake, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Takashi Oda, Koichiro Tsutsumi, Kazuhiro Nouso, Kazuya Kariyama, Hiroaki Hagihara, Akio Moriya, Motoyuki Otsuka

Gastro Hep Advances 3 ( 8 ) 1138 - 1147 2024.1

Publishing type：Research paper (scientific journal)

Background and Aims: Methods for predicting therapeutic response to immune checkpoint inhibitors in cancer therapy are in high demand. In patients with advanced hepatocellular carcinoma (HCC), atezolizumab (anti-programmed cell death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor) combination therapy (Atezo/Bev therapy) is a first-line treatment. However, no reliable biomarkers are currently available to predict its efficacy. Here, we examined serum anti-PD-1 autoantibody levels as candidate biomarkers. Methods: We prospectively enrolled 63 patients with advanced HCC who received Atezo/Bev therapy. Serum anti-PD-1 autoantibody levels were measured before treatment using an indirect enzyme-linked immunosorbent assay. The correlation between the titers and response to therapy was statistically examined. Results: Serum anti-PD-1 autoantibody levels were not significantly associated with the treatment response in any patient. However, when examining only patients who received the Atezo/Bev as their first-line therapy, higher anti-PD-1 autoantibody levels were significantly associated with worse overall survival rates. The titer was an independent risk factor for poor prognosis (odds ratio [OR] = 7.8, P = .013), in addition to a higher neutrophil-to-lymphocyte ratio (OR = 7.1, P = .009) and lower albumin levels (OR = 14.2, P = .003). Conclusion: Serum anti-PD-1 autoantibody levels correlated with the overall survival rate in patients who received Atezo/Bev as first-line therapy. Serum anti-PD-1 autoantibody levels may serve as new biomarkers for predicting the efficacy of immune checkpoint inhibitors in patients with HCC.

DOI： 10.1016/j.gastha.2024.07.018

Detection of hepatocellular carcinoma during Fontan-associated liver disease follow-up: a report of three cases Reviewed

Hideki Onishi, Norihisa Toh, Teiji Akagi, Kenji Baba, Yasuhiro Kotani, Akinobu Takaki, Shingo Kasahara, Hiroshi Ito

Clinical Journal of Gastroenterology 2023.11

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

DOI： 10.1007/s12328-023-01892-w

Other Link： https://link.springer.com/article/10.1007/s12328-023-01892-w/fulltext.html

The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab. Reviewed International journal

Yasuto Takeuchi, Kazuhiro Nouso, Shin-Ichi Fujioka, Kazuya Kariyama, Haruhiko Kobashi, Shuji Uematsu, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Shinichiro Nakamura, Kazuhisa Yabushita, Tatsuya Kikuchi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki

Cancer medicine 2023.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice. METHODS: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD. RESULTS: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). CONCLUSIONS: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice.

DOI： 10.1002/cam4.6369

Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients. Reviewed

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

Acta medica Okayama 77 ( 4 ) 377 - 385 2023.8

Language：English Publishing type：Research paper (scientific journal)

Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers - the FIB-4 index and APRI score - were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker.

DOI： 10.18926/AMO/65748

Oxidative stress-related markers as prognostic factors for patients with primary sclerosing cholangitis in Japan. Reviewed International journal

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

Hepatology international 2023.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/PURPOSE: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors. METHODS: We recruited 58 patients with PSC (mean age; 37.4 years, mean observation period; 1382 days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY). RESULTS: The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival. CONCLUSIONS: High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis.

DOI： 10.1007/s12072-023-10557-2

History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients. Reviewed

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

Acta medica Okayama 76 ( 6 ) 695 - 703 2022.12

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.

DOI： 10.18926/AMO/64120

Pathogenesis of Severe Liver Injury in Patients with Anorexia Nervosa: A Report of Two Cases and a Literature Review. Reviewed

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

The Kurume medical journal 67 ( 2.3 ) 121 - 129 2022.11

Language：English Publishing type：Research paper (scientific journal)

Anorexia nervosa (AN) can cause severe protein energy malnutrition and the consequent development of various organ disorders. AN is known to cause hepatic complications. We report two cases of starvation and refeeding-induced liver injury in patients with AN, and review the literature on the hepatic complications of AN. Acute liver injury can be induced by both starvation and refeeding, although the underlying pathomechanisms and management of liver injury differ between these two conditions. Clinicians should carefully identify the clinical features to ensure an accurate diagnosis and appropriate management of these conditions.

DOI： 10.2739/kurumemedj.MS6723011

The Colon Wall Thickness Measured Using Transabdominal Ultrasonography Is Useful for Detecting Mucosal Inflammation in Ulcerative Colitis. Reviewed

Masahiro Takahara, Sakiko Hiraoka, Masayasu Ohmori, Keiko Takeuchi, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Hideki Ohnishi, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 61 ( 18 ) 2703 - 2709 2022.9

Language：English Publishing type：Research paper (scientific journal)

Objective Transabdominal ultrasonography (TUS) is a non-invasive procedure that is reportedly useful for managing ulcerative colitis (UC) and assessing bowel wall thickness (BWT), the most common measure of mucosal inflammation. However, the exact range of BWT that reflects disease activity remains undetermined. The present study clarified the BWT due to disease activity by comparing the use of TUS in each segment of the colon versus using colonoscopy (CS) and determined the usefulness of TUS in patients with UC. Methods We divided the colon into five segments and measured the BWT using TUS. The results were then compared to the Mayo endoscopic subscore (MES) classification to determine the accuracy of BWT measurement. Patients Eighty patients with UC who underwent TUS within 14 days of CS were retrospectively registered. Results We evaluated a total of 268 images depicting each segment among 80 patients with UC. The BWT was positively correlated with endoscopic activity (0.69, p<0.0001). In each segment, the relationship between a BWT>2 mm and an MES>0 had the highest sensitivity, specificity, and accuracy (0.85-1.00, 0.67-0.92, and 0.81-0.97, respectively). Conclusion This study concluded that TUS was a useful method of detecting an MES>0, which indicates the presence of inflammation and its location among UC patients. MES>0 was found to be highly accurate when a BWT>2 mm was considered positive. This non-invasive method may help control disease activity in patients with UC.

DOI： 10.2169/internalmedicine.8827-21

Study Protocol for a Trial: A Single-Arm, Open-Labeled Study Evaluating Transcatheter Arterial Embolization Plus Everolimus Combination Therapy for Patients With Liver Metastasis of Gastroenteropancreatic Neuroendocrine Tumors. Reviewed International journal

Yasuto Takeuchi, Hironari Kato, Shigeru Horiguchi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki

Clinical Medicine Insights. Oncology 16 11795549221127750 - 11795549221127750 2022

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study. METHODS: We design a single-arm, open-label, prospective study to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastases of GEP-NETs. The study started in June 2021 at Okayama University Hospital and is expected to enroll 18 patients over a 2-year period. DISCUSSION: This study is a prospective study investigating a new treatment method for a rare disease called GEP-NETs. We may obtain useful information that contributes to the treatment guidelines in this study. However, NET is a rare disease, and although the number of cases is statistically established, it may not be possible to accurately assess causality.TRIAL REGISTRATION NUMBER: jRCT1061210015.

DOI： 10.1177/11795549221127750

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

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 15 ( 1 ) 171 - 176 2021.11

Language：English Publishing type：Research paper (scientific journal)

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

Lethal biliary congestive acute hepatitis e without acute liver failure: A case report Reviewed

Nao Yamauchi, Tetsuya Yasunaka, Akinobu Takaki, Yoshimune Hinami, Masaru Kinomura, Akina Kawahara, Takuya Adachi, Atsushi Oyama, Nozomu Wada, Yasuto Takeuchi, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

Acta Hepatologica Japonica 62 ( 8 ) 463 - 470 2021.8

Language：Japanese Publishing type：Research paper (scientific journal)

A 64-year-old man in whom benign hyperbilirubinemia had been identified was found to suffer from acute hepatitis E. Laboratory examination of the patient revealed high transaminase levels and hyperbilirubinemia, suggesting acute hepatitis, while the prothrombin time was within the normal range. The transaminase levels decreased and prothrombin time remained within the normal range; however, hyperbilirubinemia worsened to 39 mg/dl. The patient developed the complications of acute renal failure and sepsis, and eventually died. An autopsy was performed that showed no liver atrophy, liver fibrosis progression, or massive necrosis. The lung and kidney were revealed to be positive for fungal infection. The kidney was revealed to exhibit tubular conges-tion with bile. The present case offers information on the clinical course of acute hepatitis E in relatively elderly patients.

DOI： 10.2957/kanzo.62.463

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00263&link_issn=&doc_id=20210811100004&doc_link_id=10.2957%2Fkanzo.62.463&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.62.463&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma. Reviewed International journal

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 2021.6

Language：English Publishing type：Research paper (scientific journal)

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

Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan. Reviewed International journal

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

International journal of molecular sciences 22 ( 11 ) 2021.5

Language：English Publishing type：Research paper (scientific journal)

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

Abnormal fucosylation of alpha-fetoprotein in patients with nonalcoholic steatohepatitis. Reviewed International journal

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 2021.5

Language：English Publishing type：Research paper (scientific journal)

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

Prediction of the prognosis of advanced hepatocellular carcinoma by TERT promoter mutations in circulating tumor DNA. Reviewed International journal

Mami Hirai, Hideaki Kinugasa, Kazuhiro Nouso, Shumpei Yamamoto, Hiroyuki Terasawa, Yuma Onishi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Masahiro Sakata, Tetsuya Yasunaka, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

Journal of gastroenterology and hepatology 36 ( 4 ) 1118 - 1125 2021.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND ANDAIM: Human telomerase reverse transcriptase (TERT) promoter mutations were the most prevalent mutations in patients with hepatocellular carcinoma (HCC). We tried to detect the mutations with plasma circulating tumor DNA (ctDNA) in patients with advanced HCC and elucidated their clinical utility. METHODS: Circulating tumor DNA in plasma was extracted from 130 patients with advanced HCC who were treated with systemic chemotherapy (n = 86) or transcatheter arterial chemoembolization (n = 44), and TERT promoter mutations were examined with digital droplet polymerase chain reaction. The correlations between these mutations and the clinical outcome of patients were analyzed. RESULTS: Of the 130 patients examined, 71 patients (54.6%) were positive for TERT promoter mutations in ctDNA, of which 64 patients were -124bp G > A and 10 were -146bp G > A. The presence of TERT promoter mutations was correlated with large intrahepatic tumor size (P = 0.05) and high des-gamma carboxyprothrombin (P = 0.005). Overall survival of the patients with the mutations was significantly shorter than those without them (P < 0.001), and the patients with high (≥ 1%) fractional abundance of the mutant alleles showed shorter survival than those with low (< 1%) fractional abundance. Multivariate analysis revealed that TERT promoter mutation (hazard ratio [HR]: 1.94; 95% confidence interval [CI], 1.18-3.24; P < 0.01), systemic chemotherapy (HR: 2.38; 95% CI, 1.29-4.57; P < 0.01), and vascular invasion (HR: 2.16; 95% CI, 1.22-3.76; P < 0.01) were significant factors for poor overall survival. CONCLUSIONS: TERT promoter mutations in ctDNA were associated with short survival and could be a valuable biomarker for predicting the prognosis of patients with advanced HCC.

DOI： 10.1111/jgh.15227

Residual Restrictive Right Ventricular Physiology after One-and-a-Half Ventricular Repair Conversion in Pulmonary Atresia with Intact Ventricular Septum. Reviewed International journal

Kazuki Suruga, Norihisa Toh, Yasuhiro Kotani, Hideki Onishi, Teiji Akagi, Shingo Kasahara, Hiroshi Ito

CASE (Philadelphia, Pa.) 4 ( 6 ) 523 - 525 2020.12

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. Reviewed International journal

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 : the official journal of the Japan Society of Hepatology 50 ( 12 ) 1347 - 1354 2020.12

Language：English Publishing type：Research paper (scientific journal)

AIM: Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function-related markers such as urea nitrogen or creatinine. However, vascular function-related markers have not been well investigated. We investigated the effect of the vascular function-related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. METHODS: We prospectively recruited 49 patients who required add-on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1 day after tolvaptan administration. Patients exhibiting >1.5 kg weight loss after 1 week were categorized as early responders to tolvaptan. Patients were followed for a median of 200 days and were assessed for survival. RESULTS: Early responders showed lower creatinine levels (<1.0 mg/dL), and higher ADMA levels (≥0.61 nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). CONCLUSION: Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.

DOI： 10.1111/hepr.13573

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