Hepatology Research最新文献

{"title":"Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Increases in Patients With Obstructive Jaundice through the Activation of Hepatic Stellate Cells by Bile Acids.","authors":"Norihiro Ishii, Kenichiro Araki, Dolgormaa Gantumur, Ryosuke Fukushima, Takayuki Okuyama, Takaomi Seki, Haruka Okami, Kei Hagiwara, Kouki Hoshino, Shunsuke Kawai, Mariko Tsukagoshi, Takamichi Igarashi, Norio Kubo, Ken Shirabe","doi":"10.1111/hepr.14236","DOIUrl":"https://doi.org/10.1111/hepr.14236","url":null,"abstract":"<p><strong>Background: </strong>Mac-2 binding protein glycosylation isomer (M2BPGi) is a reliable serum marker for assessing liver fibrosis and is secreted by hepatic stellate cells (HSCs). However, M2BPGi is a known marker of dynamic fluctuations that reflects liver fibrosis, and factors including liver injury and hepatocyte regeneration. Obstructive jaundice (OJ) causes bile acid accumulation and subsequent liver injury. We aimed to evaluate the changes in M2BPGi levels in patients with OJ and elucidate whether HSC activation by bile acids increases M2BPGi levels.</p><p><strong>Methods: </strong>In total, 220 patients who underwent pancreatobiliary surgery were analyzed; the M2BPGi levels before and after biliary drainage were evaluated in 60 patients with OJ. Activation of HSCs (LX-2 cells) treated with bile acids (cholic acid, deoxycholic acid, and lithocholic acid) and the subsequent secretion of M2BPGi were evaluated by western blotting and coimmunoprecipitation.</p><p><strong>Results: </strong>M2BPGi levels were significantly higher in patients with OJ, strongly correlating with total bilirubin levels in laboratory data. Among the 60 patients with OJ, 51 showed decreased M2PBGi levels after biliary drainage; nine showed increased levels, even after biliary drainage. Cholangitis during biliary drainage was more common in patients with increased M2BPGi levels. Cholic acid-treated LX-2 cells upregulated α-SMA expression and M2BPGi secretion in culture media relative to non-treated LX-2 cell.</p><p><strong>Conclusions: </strong>M2BPGi levels are significantly higher in patients with than without OJ due to the activation of HSCs by bile acids. M2BPGi levels are improved by biliary drainage, and the presence of prolonged liver dysfunction, and inflammation (such as cholangitis) appears to induce prolonged M2BPGi elevation.</p><p><strong>Trial registration: </strong>HS2023-100.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to ''Circulating Myostatin Levels as a Prognostic Biomarker in Patients With Acute Liver Failure and Late-Onset Hepatic Failure''.","authors":"Manabu Hayashi, Kazumichi Abe, Hiromasa Ohira","doi":"10.1111/hepr.70000","DOIUrl":"https://doi.org/10.1111/hepr.70000","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus.","authors":"Taeang Arai, Masanori Atsukawa, Chikako Nagao, Zento Yamada, Takahiro Rokugo, Kenta Suzuki, Michika Kitamura, Tetsuyuki Higashi, Kaori Koyano, Yuta Hasegawa, Tadamichi Kawano, Hiroki Ono, Yuji Yoshida, Tomomi Okubo, Korenobu Hayama, Ai Nakagawa-Iwashita, Norio Itokawa, Chisa Kondo, Mototsugu Nagao, Masato Iwabu, Katsuhiko Iwakiri","doi":"10.1111/hepr.14241","DOIUrl":"https://doi.org/10.1111/hepr.14241","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to clarify the impact of tirzepatide as a treatment for Type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>This single-arm, prospective, observational pilot study included 16 patients with MASLD and T2DM who were treated with tirzepatide. Of these, 13 patients completed 48 weeks of treatment. Tirzepatide was initiated at a dose of 2.5 mg once weekly for 4 weeks, and dose adjustments were left to the discretion of the attending physician based on efficacy and adverse events.</p><p><strong>Results: </strong>Significant improvements in body weight, liver enzymes, and hemoglobin A1c were found at Week 12 and were sustained throughout the 48-week treatment period compared with baseline values (all p < 0.05). Controlled attenuation parameter significantly decreased from baseline to 48 weeks (p < 0.05). Changes in body weight were correlated with changes in alanine aminotransferase levels (r = 0.57, p < 0.05) but not with changes in controlled attenuation parameter (r = 0.45, p = 0.12). The results of noninvasive tests for fibrosis, including Type IV collagen 7s, Wisteria floribunda agglutinin-positive Mac-2-binding protein, the fibrosis-4 index, and the liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.05). Most adverse events were transient Grades 1-2 gastrointestinal symptoms, including nausea (5 patients, 31.3%), diarrhea (3 patients, 18.8%), and constipation (2 patients, 12.5%).</p><p><strong>Conclusions: </strong>Tirzepatide treatment for T2DM in patients with MASLD significantly improved liver steatosis and injury, surrogate markers of liver fibrosis, and diabetes status, and reduced body weight.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging-Based Surveillance of Gastroesophageal Varices in Fontan-Associated Liver Disease: Toward a Noninvasive Strategy.","authors":"Tadashi Namisaki, Akihiko Shibamoto, Kosuke Kaji, Hitoshi Yoshiji","doi":"10.1111/hepr.14239","DOIUrl":"https://doi.org/10.1111/hepr.14239","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to ''Circulating Myostatin Levels as a Prognostic Biomarker in Patients With Acute Liver Failure and Late-Onset Hepatic Failure''.","authors":"Yanyan Zhang, Juanjuan Zhang","doi":"10.1111/hepr.14242","DOIUrl":"https://doi.org/10.1111/hepr.14242","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Possible Telomerase Reverse Transcriptase Promoter Mutation in Human Chemically Induced Liver Progenitors.","authors":"Baglan Askeyev, Akihiko Soyama, Daisuke Miyamoto, Kayo Hasegawa, Hajime Matsushima, Takanobu Hara, Takashi Hamada, Kazushige Migita, Takuro Fujita, Hajime Imamura, Mampei Yamashita, Tomohiko Adachi, Susumu Eguchi","doi":"10.1111/hepr.14240","DOIUrl":"https://doi.org/10.1111/hepr.14240","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to investigate the presence of telomerase reverse transcriptase (TERT) promoter mutations in human chemically induced liver progenitors (hCLiPs) and to evaluate their potential association with carcinogenesis.</p><p><strong>Methods: </strong>TERT promoter mutations were analyzed in 20 formalin-fixed, paraffin-embedded HCC samples, 19 liver cirrhosis (LC) samples, and five hCLiPs derived from cirrhotic liver tissue. Genomic DNA was extracted, and droplet digital PCR was performed to detect TERT promoter mutations (C228T and C250T).</p><p><strong>Results: </strong>No TERT promoter mutations were detected in hCLiPs or LC samples. In contrast, 11 of 20 (55%) HCC samples carried the C228T mutation, with mutant allele frequencies ranging from 2.7% to 28.0% (mean ± SD: 21.6 ± 11.05%). The C250T mutation was not identified in any sample.</p><p><strong>Conclusion: </strong>These findings show that hCLiPs reprogrammed using small molecules do not harbor TERT promoter mutations, supporting their genomic stability and potential safety for clinical applications.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extrahepatic Events in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and the Impact of Genetics and Alcohol Intake.","authors":"Tomomi Kogiso, Yuri Ogasawara, Makiko Taniai, Katsutoshi Tokushige, Yousuke Nakai","doi":"10.1111/hepr.14233","DOIUrl":"https://doi.org/10.1111/hepr.14233","url":null,"abstract":"<p><strong>Aims: </strong>The Delphi consensus established new criteria for steatotic liver disease (SLD), but the extrahepatic complications in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. In this study, we investigated the clinical course of MASLD patients compared to those with MASLD and increased alcohol intake (MetALD) and alcohol-associated liver disease (ALD).</p><p><strong>Methods: </strong>A total of 1150 Asian patients with SLD were enrolled and categorized into the MASLD (n = 803), MetALD (n = 81), and ALD (n = 266) groups. The incidence levels of extrahepatic malignancies and cardiovascular disease (CVD) events were compared among the three groups. Genetic alterations in PNPLA3, HSD17B13, GCKR, and GDF15 were analyzed in 201 MASLD cases.</p><p><strong>Results: </strong>MASLD patients were significantly younger (MASLD, MetALD, ALD; 53, 65, and 62 years), had a lower proportion of males (49.3%, 82.7%, and 86.8%), and had a higher BMI (26.7, 24.1, and 22.6 kg/m²) than MetALD and ALD patients. During a median follow-up of 10.6 years, the proportions of patients who developed extrahepatic malignancies were 7.2%, 9.9%, and 5.6%, and those who experienced CVD events were 5.7%, 3.7%, and 4.1% in the MASLD, MetALD, and ALD groups, respectively. However, Cox proportional hazards analysis revealed no significant difference in the risk of extrahepatic complications among the groups after adjusting for baseline characteristics. A single nucleotide polymorphism in PNPLA3 was associated with the development of CVD events in MASLD patients.</p><p><strong>Conclusions: </strong>Extrahepatic events were observed at similar rates among patients with SLD after adjusting for confounding factors. However, overall mortality and the risk of HCC were significantly higher in the MetALD and ALD groups.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Gene Mutation Analysis Through Post-Ablation Liver Tumor Biopsy Specimens.","authors":"Tasuku Nakabori, Yoji Kukita, Hidetoshi Satomi, Kaori Mukai, Minoru Shigekawa, Shigenori Nagata, Kazuyoshi Ohkawa","doi":"10.1111/hepr.14237","DOIUrl":"https://doi.org/10.1111/hepr.14237","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Glucose Intolerance a Precursor of Cachexia in Patients With Liver Cirrhosis?","authors":"Tsutomu Nishida, Satoru Okabe, Akira Doi, Kengo Matsumoto","doi":"10.1111/hepr.14235","DOIUrl":"https://doi.org/10.1111/hepr.14235","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Alpha-Fetoprotein/Hepatocyte Growth Factor Ratio as a Novel Biomarker Predicting the Prognosis of Acute Alcoholic Hepatitis: Need of Validation and Dynamic Assessment to Establish Utility.","authors":"Ajay Kumar Mishra","doi":"10.1111/hepr.14234","DOIUrl":"https://doi.org/10.1111/hepr.14234","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}