Journal of Hepatology最新文献

{"title":"Stratification, Therapeutic Targeting and Towards Personalised Care in Cirrhosis.","authors":"Nipun Verma, Paolo Angeli, Rajiv Jalan","doi":"10.1016/j.jhep.2025.07.012","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.07.012","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From HCV to HEV: Repurposing a nucleoside analogue for hepatitis E therapy","authors":"Lisa Sandmann","doi":"10.1016/j.jhep.2025.06.022","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.06.022","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Background and context</h2>Hepatitis E virus (HEV) infection is a substantial public health burden leading to approximately 20 million acute infections per year. The majority of infections are self-limiting, but relevant risks remain for pregnant women and immunocompromised patients, in whom HEV infection is associated with acute liver failure and chronic HEV infection, respectively.¹ HEV genotypes 1 (HEV-1) and 2 (HEV-2) are highly prevalent in low-income Asian and African countries, transmission occurs faecal-orally,</section></section><section><section><h2>Objectives, methods and findings</h2>The study by Zhang and colleagues investigated the antiviral effect of nucleoside analogues, originally developed against the hepatitis C virus (HCV), on HEV.⁸ Of the 19 different sugar-modified guanosine analogues tested, JNJ-9117 exhibited the most potent, broad-spectrum, <em>in vitro</em> antiviral activity against HEV-1, HEV-3, and rat HEV in various cell lines, including primary human hepatocytes and non-hepatic cell lines. Comparisons with ribavirin and sofosbuvir – an HCV polymerase inhibitor</section></section><section><section><h2>Significance of findings</h2>The study published by Zhang <em>et al.</em> demonstrates the <em>in vitro</em> and <em>in vivo</em> efficacy of JNJ-9117 in treating HEV infection, with a high resistance barrier and good tolerability in the animal model. JNJ-9117 was originally developed as a direct-acting antiviral to treat HCV infection, as it targets the viral polymerase. The imperative structural motifs of the catalytic site of the RdRp are comparable between HCV, HEV 1-4 and rat HEV, explaining the antiviral efficacy of JNJ-9117 in both HCV and</section></section><section><section><h2>Financial support</h2>The authors did not receive any financial support to produce this manuscript.</section></section><section><section><h2>Conflict of interest</h2>The authors of this study declare that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"149 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin and rifaximin in patients with decompensated cirrhosis: Still a place for LIVER HOPE?","authors":"Marika Rudler","doi":"10.1016/j.jhep.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.06.023","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Background and context</h2>In patients with cirrhosis, prognosis is primarily determined by the development of portal hypertension-related decompensation.¹ Acute-on-chronic liver failure (ACLF) defined by the concomitant occurrence of decompensation and organ failure, is associated with worse prognosis than decompensation alone.² Once decompensation occurs, clinical management should address both the current decompensation event(s) and the prevention of further decompensation, as defined by Baveno VII.³ Both</section></section><section><section><h2>Objectives, methods and findings</h2>In the LIVERHOPE phase III trial,⁹ patients with decompensated cirrhosis were assigned to receive simvastatin 20 mg/day and rifaximin 1,200 mg/day (n = 117), or placebo (n = 120) for 12 months, stratified according to Child-Pugh class. The primary endpoint was incident ACLF, and secondary outcomes included transplant or death and a composite endpoint of complications of cirrhosis (ascites, hepatic encephalopathy, acute variceal bleeding, acute kidney injury, and infection). Overall, there was</section></section><section><section><h2>Significance of findings</h2>This large multicenter international randomized controlled trial (RCT) unfortunately failed to demonstrate any efficacy of the combination of simvastatin 20 mg/day and rifaximin 1,200 mg/day for the prevention of ACLF and further decompensation in patients with decompensated cirrhosis. The rationale for the use of simvastatin relied on its role in reducing portal hypertension, and a survival benefit in patients with a history of acute variceal bleeding.¹⁰ However, the baseline characteristics</section></section><section><section><h2>Financial support</h2>The authors did not receive any financial support to produce this manuscript.</section></section><section><section><h2>Conflict of interest</h2>Gore, Abbvie, Gilead.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"9 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A newly revealed signaling pathway may explain the conundrum of how FGF21 simultaneously increases insulin sensitivity and autophagy","authors":"Timothy Rolph, Morris J. Birnbaum","doi":"10.1016/j.jhep.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.07.002","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Financial support</h2>The authors did not receive any financial support to produce this manuscript.</section></section><section><section><h2>Authors’ contributions</h2>Both authors contributed equally to this editorial.</section></section><section><section><h2>Conflict of interest</h2>Timothy Rolph is an employee of Akero Therapeutics Inc.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"24 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP/TAZ-Driven Cell Competition in Early MASLD as a Tumor-Suppressive Mechanism","authors":"Amaya López-Pascual, Maite G. Fernández-Barrena, Matías A. Avila","doi":"10.1016/j.jhep.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.07.009","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Funding:</h2>Work in the authors’ laboratory is funded by: Grants from Ministerio de Ciencia Innovación y Universidades MICINN-Agencia Estatal de Investigación integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER PID2022-136616OB-I00/AEI/10.13039/501100011033 (MAA), PID2020-117116RB-I00 (MGFB). Grant ASPIRE-AECC RETOS245779LLOV, and Coordinated Grant PRYCO223102ARM from the Scientific Foundation of the Spanish Association Against Cancer (AECC) (MAA,</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"57 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rivaroxaban to prevent complications of portal hypertension in cirrhosis: The CIRROXABAN study","authors":"Ángela Puente, Fanny Turón, Javier Martínez, Jose Ignacio Fortea, Manuel Hernández Guerra, Edilmar Alvarado, Mónica Pons, Marta Magaz, Elba Llop, Carmen Alvarez-Navascués, Alberto Amador Navarrete, Marina Berenguer, Helena Masnou, Rafael Bañares, Marta Casado, Javier Ampuero, José Rios, Carolina Saavedra, Annabel Blasi, Ton Lisman, Juan Carlos Garcia-Pagán","doi":"10.1016/j.jhep.2025.06.035","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.06.035","url":null,"abstract":"<h3>Background &amp; Aims</h3>Previous studies suggested that anticoagulation decreases the probability of developing portal hypertension (PHT)-related complications and improves survival in cirrhotic patients. Our study aimed to evaluate the efficacy/safety of the direct anticoagulant rivaroxaban in patients with cirrhosis.<h3>Methods</h3>Randomized, double-blind, placebo-controlled multicenter trial in cirrhotic patients with PHT and moderate liver dysfunction (Child-Pugh:7-10) of rivaroxaban 10mg/24 hours vs. placebo for 24 months. Primary composite endpoint: development of PHT-related complication or death/transplantation whatever occurred first. A modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. This trials was registered with Clinical Tria.gov with number NCT02643212 and EudraCT Number: 2014-005523-27<h3>Results</h3>90 patients (49 placebo and 41 rivaroxaban) were included<strong>.</strong> After a median follow-up period of 10.1 months, 34 patients developed the primary endpoint, 23 (46.9%) in the placebo vs 11 (26.8%) in the rivaroxaban group, with an observed cumulative probability of survival free of primary endpoint at 1 and 2 years of 54.4% and 43% in placebo vs 78.7 and 67.1 % in rivaroxaban (Log-rank; p=0.058). In a post-hoc analysis a potentially beneficial effect of rivaroxaban was observed in Child-Pugh B7 patients (n=55) HR (95%CI 0.258 [0.074 to 0.900]). In the PP analysis (41 placebo and 37 rivaroxaban), the main event was reached in 19 placebo (46.3%) vs. 9 (24.3%) in the rivaroxaban group HR (95%CI 0.463 [0.209 to 1.024]).Non-PHT related bleeding events occurred more frequently in patients receiving rivaroxaban (36.6% vs 14.3%) RR (95%CI): 2.56 (1.16; 5.67). However, no differences were observed in major bleeding events.<h3>Conclusions</h3>In cirrhotic patients with moderate liver dysfunction, rivaroxaban may improve PHT complication-free survival without significantly increasing major bleeding events.<h3>Impact and implications</h3>This study provides novel evidence of the potential use of rivaroxaban to prevent liver decompensation in cirrhotic patients with portal hypertension. The observed reduction in decompensation events aligns with previous findings on anticoagulation in cirrhosis, suggesting a potential therapeutic role for rivaroxaban in this population. Although the reduction of the primary endpoint did not reach statistical significance in the whole cohort, this potential effect was observed in a post hoc analysis in Child-Pugh B patients; however, these findings should be interpreted with caution due to the exploratory and post hoc nature of the subgroup analyses. Non portal hypertension related bleeding was overall increased in patients receiving rivaroxaban but not those that were classified as severe. These findings underscore the need for further investigation into optimal dosing strategies to maximize efficacy while minimizing bleeding risks.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"96 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The barriers for uptake of artificial intelligence in hepatology and how to overcome them","authors":"Jan Clusmann, Maria Balaguer-Montero, Octavi Bassegoda, Carolin V. Schneider, Tobias Seraphin, Ellis Paintsil, Tom Luedde, Raquel Perez Lopez, Julien Calderaro, Stephen Gilbert, Thomas Marjot, Ashley Spann, Debbie L. Shawcross, Sabela Lens, Eric Trépo, Jakob Nikolas Kather","doi":"10.1016/j.jhep.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.07.003","url":null,"abstract":"Artificial intelligence (AI) methods in hepatology have proliferated since the mid-2010s, with numerous publications and some regulatory approvals. Yet, adoption of AI methods in real-world clinical practice and clinical research remains limited. Despite clear benefits of using AI to analyze complex data types in hepatology, such as histopathology, radiology images, multi-omics and more recently, natural language patient data, there are still substantial barriers and challenges to its integration into routine clinical workflows. Here, we assess limitations and propose a set of clear recommendations both for the AI systems as well as for the environment of hepatology to ease transition of AI-based diagnostic, prognostic or predictive systems into clinical care. In particular, we argue that the use of AI in clinical trials, seamless integration into hospital information systems and building AI literacy among clinicians will ultimately drive clinical adoption. We validate this perspective through a Delphi consensus involving 34 international experts from hepatology, AI, and data science, ensuring a comprehensive and consensus-driven evaluation of our recommendations.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"108 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cells drive CCR5+CD4+ tissue-resident memory T cell cytotoxicity via IL-15Rα-IL-15 signaling in primary biliary cholangitis","authors":"Xiting Pu, Yuyang Liu, Zhuwan Lyu, Yujie Zhou, Yudong Zhao, Bingyuan Huang, Qiyun Xia, Yi Wu, Jun Qian, Ruqi Tang, Min Lian, Xiong Ma, Zhengrui You","doi":"10.1016/j.jhep.2025.06.037","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.06.037","url":null,"abstract":"<h3>Background &amp; Aims</h3>IL-15Rα mediates immune responses by binding and trans-presenting IL-15 to tissue-resident memory T (T_RM) cells, enabling sustained activation. Given the pivotal role of IL-15Rα/IL-15 signaling in autoimmune diseases, elucidating its organ-specific expression and pathogenic functions in primary biliary cholangitis (PBC) remains crucial.<h3>Methods</h3>Immunohistochemical staining was performed on liver tissues from patients with PBC (n=94), AIH (n=32), CHB (n=10), NASH (n=7) and HCs (n=10) to assess IL-15Rα expression. Flow cytometric analysis characterized intrahepatic IL-15Rα⁺ B cells and CD4⁺ T_RM cells .RNA-Seq was employed to delineate the transcriptomic signatures of in vitro-induced B cells and intrahepatic leukocytes. To investigate the cytotoxicity of T_RM cells against cholangiocytes, we performed organoid co-culture system. Moreover, dnTGFβRII mice treated with anti-IL-15/IL-15Rα mAb were used for in-vivo validation.<h3>Results</h3>IL-15Rα⁺ cells were significantly increased in PBC patients, primarily concentrated within the plasmablast B cell population, and positively correlated with hepatic inflammation severity. IL-15Rα⁺ B cells enriched around bile ducts in PBC livers secrete CCL3 to recruit CCR5⁺CD4⁺ T_RM cells, enhancing their effector functions via IL-15Rα/IL-15 signaling. Notably, CCR5⁺CD4⁺ T_RM cells drive cholangiocyte pyroptosis through granzyme A-mediated GSDMB cleavage. Furthermore, blockade of IL-15Rα/IL-15 signaling ameliorates liver injury in PBC mouse models.<h3>Conclusions</h3>Our findings reveal an important pathogenic mechanism in PBC wherein IL-15Rα⁺ B cells contribute to biliary injury by activating CCR5⁺CD4⁺ T_RM cells. This mechanism likely works in concert with other immune effector pathways in driving disease progression.<h3>Impact and implications</h3>This study reveals that IL-15Rα-expressing B cells manifest a pro-inflammatory phenotype and promote biliary injury by impairing immune homeostasis through aberrant activation of tissue-resident memory T cells during PBC progression. Although we now offer a new paradigm how IL-15 trans-presentation is regulated in a B cell-dependent manner in PBC, the regulatory effects of IL-15Rα/IL-15 signaling on other chronic liver diseases remain to be further elucidated.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"4 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of N-glycosylation via leucine-activated leucyl-tRNA synthetase 1 overcomes chemoresistance in intrahepatic cholangiocarcinoma","authors":"Haining Liu, Jianlei Wang, Yong Yao, Tong Xia, Shuqian Zhang, Ling Pan, Xin Qin, Zeyang Liu, Huaikun Wang, Mingkun Liu, Sai Zhang, Zhengnan Zhao, Mengfan Yang, Yi Gao, Gang Du, Wei Wang, Yanfeng Liu, Jingxin Li, Bin Jin","doi":"10.1016/j.jhep.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.07.008","url":null,"abstract":"<h3>Background &amp; Aims</h3>Intrahepatic cholangiocarcinoma (ICC) is a highly lethal liver malignancy with poor response rates to chemotherapy. Although translational reprogramming is a recognised hallmark of therapy resistance, its role in ICC remains unclear. This study aimed to investigate codon-biased translation in ICC chemoresistance and explore potential therapeutic strategies.<h3>Methods</h3>Proteomic data and tumour specimens were utilized to identify key proteins associated with prognosis in ICC. Functional analyses and mechanistic studies were conducted using cell cultures, conditional knockout mouse models, and two hydrodynamic transfection ICC models. N-glycoproteomics, polysome profiling, and ribosome-nascent chain sequencing (RNC-seq) were employed to uncover the downstream translational effects. Leucine supplementation was used to target LARS1 to improve chemotherapy efficacy.<h3>Results</h3>Leucyl-tRNA Synthetase 1 (LARS1) was significantly downregulated in ICC, particularly in advanced-stage tumours, and positively correlated with patient survival. Using diverse ICC models, we demonstrated that LARS1 played a pivotal role in regulating ICC chemoresistance. LARS1 depletion impaired leucyl-tRNA charging and selectively reduced translation of N-glycan biosynthesis enzymes (ALG3, RFT1, and ALG12) via codon-biased hypotranslation. This led to impaired N-glycosylation of ABCC1, thereby enhancing drug efflux activity and promoting chemoresistance. Conversely, exogenous leucine supplementation restored LARS1 expression, rescued the translation of N-glycan biosynthesis enzymes, and markedly improved gemcitabine–oxaliplatin efficacy.<h3>Conclusions</h3>This study uncovers a novel mechanism of LARS1-dependent codon-biased translation underling ICC chemoresistance. It further establishes leucine supplementation as a feasible, and potentially translational strategy to improve the efficacy of ICC chemotherapy.<h3>Impact and Implications</h3>This study demonstrates that LARS1 downregulation disrupts N-glycan biosynthesis and enhances ABCC1-mediated chemoresistance in ICC. Our findings are important for oncologists and translational researchers, as they identify LARS1-dependent codon-biased translation as a critical determinant of chemotherapy response in ICC. Practically, we uncover that exogenous leucine supplementation restores LARS1 levels and synergises with gemcitabine–oxaliplatin treatment, offering a safe dietary intervention to overcome chemoresistance. These implications are firmly based on preclinical evidence, although future clinical trials are needed to validate the safety and efficacy of leucine supplementation strategies in ICC patients.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"14 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Join the community and become an EASL member today!","authors":"","doi":"10.1016/S0168-8278(25)02288-3","DOIUrl":"10.1016/S0168-8278(25)02288-3","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 2","pages":"Page iii"},"PeriodicalIF":26.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}