Journal of Hepatology最新文献

{"title":"Recompensation in alcohol related liver disease -more snakes and ladders than stygian slide.","authors":"Jack Baker, James O'Beirne","doi":"10.1016/j.jhep.2026.03.016","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.03.016","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486276","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 the Editor’s Desk...","authors":"Philip N. Newsome, Frank Tacke, Heiner Wedemeyer, Lorenza Rimassa, Annalisa Berzigotti, Tom H. Karlsen, Vlad Ratziu","doi":"10.1016/j.jhep.2026.01.010","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.01.010","url":null,"abstract":"<h2>Section snippets</h2><section><section><section><h2>Microbial metabolic derailment as a hidden driver of liver injury after TACE</h2>Transarterial chemoembolization (TACE) is a widely used locoregional therapy for hepatocellular carcinoma (HCC) that achieves tumour control through ischaemic necrosis and local chemotherapy delivery. Despite its overall safety, TACE causes clinically relevant liver injury in more than 20% of patients, including rare cases of liver failure, underscoring persistent challenges in predicting treatment tolerance and limiting non-selective damage to healthy liver tissue. Using integrated microbiome</section></section></section><section><section><section><h2>DNAJ–PKAc–driven glutamine addiction in fibrolamellar HCC</h2>Fibrolamellar carcinoma (FLC) presents a significant clinical challenge as a rare, aggressive liver cancer primarily affecting young people and driven by a recurrent ‘undruggable’ DNAJ-PKAc protein fusion, for which no standard effective treatment currently exists. Through integrated transcriptomic, metabolomic, and functional analyses, <span><span>Kamdar and coworkers</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> delineate a metabolic vulnerability in FLC driven by the pathognomonic DNAJ–PKAc fusion, which promotes glutamine flux into cancer cells to</section></section></section><section><section><section><h2>Consensus position statements for the standardized application of histological grading and staging systems in MASH clinical trials</h2>A landmark reference document, developed by a group of 25 liver pathology experts, for all involved with metabolic dysfunction-associated steatotic liver disease (MASLD) research, is presented in the current issue. After a series of workshops and an associated Delphi process, <span><span>Lackner, Gouw, and coworkers</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> present an extensive outline and updated guidance for the histological assessment of liver biopsies in clinical trials and criteria for histological MASLD grading and staging. Furthermore, the</section></section></section><section><section><section><h2>Characterization of ferroportin disease and SLC40A1-related hemochromatosis – results from the EASL non-HFE registry</h2>Over the last 10 years, EASL has supported a number of patient registries. Particularly in the rare disease field these registries have supported important research activities. As an example of this, <span><span>Troppmair and coworkers</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"107 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471125","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 EASL Congress 2026 will take place 27-30 May in Barcelona (Spain). Register now!","authors":"","doi":"10.1016/s0168-8278(26)00091-7","DOIUrl":"https://doi.org/10.1016/s0168-8278(26)00091-7","url":null,"abstract":"No Abstract","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"6 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471126","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":"Systemic assessment via Cardiovascular-Kidney-Metabolic (CKM) staging complements the longitudinal evaluation of liver stiffness in MASLD","authors":"Weicheng Lai, Shenshen Du, Liangxiu Wu, Boda Zhou","doi":"10.1016/j.jhep.2026.03.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.03.011","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>Authors' contributions WL and SD contributed equally to this work as co-first authors. WL and SD conceived the study, performed the data analysis, and drafted the manuscript. LW contributed to the interpretation of data. BZ supervised the study and critically revised the manuscript. All authors approved the final version.</section></section><section><section><h2>Data availability statement</h2>UK Biobank data are available to bona fide researchers upon application to the UK Biobank (<span><span>https://ukbiobank.dnanexus.com/landing</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>). The present analyses were conducted under approved access.</section></section><section><section><h2>Financial support</h2>This work was supported by <span>National Natural Science Foundation of China</span> (<!-- -->32470826<!-- -->), and <span>Beijing Municipal Health Commission</span> (<!-- -->2024-3-034<!-- -->).</section></section><section><section><h2>Conflict of interest</h2>None.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"9 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448367","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":"An immunocompetent murine model of virus-elicited liver fibrosis and hepatocellular carcinoma","authors":"Mariana Nogueira Batista, Juliano Bordignon, Ana Luiza Pamplona Mosimann, Tesia Bobrowski, Hsuan-An Chen, Gabriel Tobin-Xet, Erika Ashihara Barrall, Nataliya Prokhnevska, Abishek Balachandra Vaidya, Tyler Lewy, Kenneth Harold Dinnon, Leon Louis Seifert, Briana Zeck, Corrine Quirk, Yu-Jui Ho, Aveline Filliol, Raphael Wolfisberg, Caroline Jiang, Bruno Cogliati, Luis Chiriboga, Charles Moen Rice","doi":"10.1016/j.jhep.2026.02.020","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.02.020","url":null,"abstract":"<h3>Background &amp; Aims</h3>Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Over 75% of HCC cases are associated with chronic viral infections. Mechanistic studies and preclinical therapeutic development for virus-associated HCC have been limited by a paucity of small animal models of chronic hepatotropic virus infection that faithfully recapitulate human disease.<h3>Methods and Results</h3>Here we demonstrate the induction of chronic hepatitis, progressive liver fibrosis, and HCC in immunocompetent laboratory mice upon chronic viral infection with Norway rat hepacivirus (NrHV) - a virus closely related to hepatitis C virus (HCV). NrHV-elicited tumors resemble HCV-associated tumors and liver transcriptome analyses reveal numerous similarities between chronic NrHV and HCV.<h3>Conclusions</h3>These findings establish an experimentally tractable, physiologically relevant, and immunocompetent mouse model of virus-elicited progressive liver fibrosis and oncogenesis.<h3>Impact and implications</h3>(lay summary); The NrHV-HCC model represents the first immunocompetent infectious system that faithfully recapitulates the multistage progression from chronic viral hepatitis to spontaneous hepatocellular carcinoma, bridging a long-standing translational gap between mechanistic mouse studies and human liver cancer. By mirroring the immunopathological, molecular, and sex-associated features of chronic HCV infection, this model provides an unparalleled platform to investigate virus-host interactions underlying fibrosis and oncogenesis. High HCC penetrance and the genetically tractable C57BL/6 background further enhance experimental utility, enabling precise mechanistic dissection and genetic manipulation in a physiologically relevant setting. The capacity to study spontaneous tumor development in the context of natural infection allows for rigorous testing of antifibrotic and anti-cancer strategies, while the persistence of oncogenic potential after viral clearance raises important questions about irreversible disease reprogramming and elevated cancer risk following viral cure - issues of direct relevance to patients cured of HCV.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"15 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439880","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":"Is Partial Cure a Realistic Endpoint for Novel Hepatitis B Therapy? Reply to Chan et al.","authors":"Milan J. Sonneveld, Harry L.A. Janssen","doi":"10.1016/j.jhep.2026.03.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.03.009","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"34 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447389","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":"Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges: Tissue-specific PNPLA3 lipid remodeling.","authors":"Panyun Wu, Yang Wang, Jonathan C Cohen, Helen H Hobbs","doi":"10.1016/j.jhep.2026.02.029","DOIUrl":"10.1016/j.jhep.2026.02.029","url":null,"abstract":"<p><strong>Background & aims: </strong>PNPLA3(I148M) is the strongest genetic risk factor for steatotic liver disease (SLD), but its functional role and tissue-specific regulation remain unclear. Pnpla3 mRNA levels are significantly higher in mouse adipose tissue than liver, yet its role in adipose tissue is not known. Here, we characterize the molecular mechanisms underlying tissue-specific differences in PNPLA3 expression in mice to clarify its functional role and link to SLD risk.</p><p><strong>Methods: </strong>Pnpla3 mRNA and PNPLA3 protein levels were quantified in liver and adipose depots of fasted and refed mice at 30°C and 6°C. Signaling pathways regulating PNPLA3 expression in adipocytes were examined using adrenergic agonists and pathway-specific modulators. Translation and proteasomal inhibitors were used during adrenergic stimulation to investigate the discordance between Pnpla3 mRNA and protein levels. Relationship between PNPLA3 levels and triglyceride (TG) fatty acid composition was also assessed.</p><p><strong>Results: </strong>At thermoneutrality, feeding strongly increased PNPLA3 levels in liver but it remained undetectable in adipose tissue. Conversely, cold exposure or β3-adrenergic stimulation had no effect on hepatic PNPLA3, but increased PNPLA3 >19-fold in brown adipose tissue (BAT), despite causing a >75% reduction in Pnpla3 mRNA, indicating robust post-translational regulation. In BAT, adrenergic signaling via cAMP/PKA and PI3K/AKT elevated PNPLA3 by reducing proteasomal degradation. PNPLA3 expression correlated with depletion of TG-long-chain polyunsaturated fatty acids (TG-LCPUFAs) in both liver and BAT, consistent with a role in lipid remodeling.</p><p><strong>Conclusions: </strong>These findings reveal striking tissue- and context-specific regulation of PNPLA3, but a conserved association between its expression and TG-LCPUFAs levels, suggesting that PNPLA3 modulates lipid remodeling in response to metabolic stress and that disrupting this function may contribute to SLD susceptibility.</p><p><strong>Impact and implications: </strong>Despite being the strongest genetic risk factor for SLD, PNPLA3's physiological role remains unclear. Using mouse models, this study reveals that PNPLA3 is regulated in a tissue-specific manner in response to feeding and cold exposure, thereby promoting remodeling of cellular lipids to adapt to dietary and environmental challenges. The localization of PNPLA3 action and its tissue-specific regulation are directly relevant to hepatologists and metabolic researchers aiming to understand its influence on intracellular lipid composition and its effects on disease susceptibility. Moreover, modulation of PNPLA3 turnover-and its impact on LCPUFAs remodeling-emerges as a potential therapeutic strategy for regulating lipid homeostasis in SLD.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390259","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":"BCLC classification and AI-based image quantification: What is meant to be will come together – but how and when?: BCLC and AI-based image quantification","authors":"Lukas Müller, Jakob N. Kather, Jens U. Marquardt, Maria Reig, Qiang Wang, Daniel Pinto dos Santos, Roman Kloeckner","doi":"10.1016/j.jhep.2026.02.027","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.02.027","url":null,"abstract":"The Barcelona Clinic Liver Cancer (BCLC) classification has been the mainstay for prognostic assessment and initial treatment selection in hepatocellular carcinoma (HCC) for more than two decades. It is widely clinically accepted and has been reaffirmed in the recently renewed European Association for the Study of the Liver (EASL) Clinical Practice Guidelines on the management of HCC. Its design is based on simple clinical and imaging parameters, which makes it highly applicable in clinical routine. However, it does not fully utilize all information, which is potentially encoded in routine radiology imaging. With artificial intelligence (AI) methods now maturing, we have a robust way to extract and quantify digital imaging features fully automatically without much user input and with high precision. Therefore, AI could bridge quantitative imaging into clinical decision-making, together with the existing BCLC classification. However, despite substantial AI advancements in many fields such as automated tumor volumetry, radiomics, detection of metastatic lesions, and even capturing opportunistic imaging biomarkers, a translational gap persists. While challenges related to technical, administrative, and cost-related, but also training-related factors have to be taken into account, a certain aversion to change, as well as absence of standardized AI validation and missing workflow integration hamper the clinical implementation in routine care. This article aims to evaluate current AI-quantified imaging parameters and their potential for synergy with the established BCLC classification.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"46 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371310","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":"Distinct molecular pathways regulated by activated AKT and YAP signaling during intrahepatic cholangiocarcinoma progression","authors":"Jinqiu Zhao, Lian Yang, Yujia Qin, Yi Zhang, Tingjie Wang, Jingwen Wang, Rui Liao, Benjamin Green, Guofei Cui, Weiting Liao, Yu Qiao, Meng Xu, Hua Yang, Christine Farrar, Bing Liang, Xiaosong Li, Xiaojuan Xin, Xiang Li, Diego F. Calvisi, Xue Wang, Youping Deng, Yanhui Wu, Xin Chen","doi":"10.1016/j.jhep.2026.02.025","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.02.025","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"45 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360552","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":"Kupffer cell plasticity regulates hepatic immunity in mycobacterial infection","authors":"Jana Neuber, Florens Lohrmann, Samuel Wald, Merve Göçer, Anne Kathrin Lösslein, David Obwegs, Manuel Rogg, Vitka Gres, Julia Kolter, Torsten Goldmann, Kerstin Walter, Christoph Hölscher, Christoph Schell, Sebastian Preissl, , Philipp Henneke","doi":"10.1016/j.jhep.2026.02.024","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.02.024","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"52 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360553","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}