Journal of Hepatology最新文献

{"title":"Anti-TNF therapies in autoimmune hepatitis: promises and challenges.","authors":"Marte Lie Høivik, Herbert Tilg","doi":"10.1016/j.jhep.2026.04.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.011","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816256","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":"Scoring breakthroughs at Villa Park: David Adams and the science of rolling liver lymphocytes.","authors":"Tom Hemming Karlsen","doi":"10.1016/j.jhep.2026.04.015","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.015","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816290","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":"Uncovering immune dysfunction in ACLF: cellular mechanisms, molecular pathways, and therapeutic frontiers.","authors":"Marti Ortega-Ribera, Robert Brenig, Christine Bernsmeier, Gyongyi Szabo","doi":"10.1016/j.jhep.2026.04.025","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.025","url":null,"abstract":"<p><p>Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by acute hepatic decompensation, multi-organ failure, and high short-term mortality in patients with liver cirrhosis. A hallmark of ACLF is profound deterioration of the immune system, which contributes to organ-specific excessive inflammation and immune dysfunction, predisposing patients to infection and multi-organ failure. This review aims to elucidate the cellular and molecular mechanisms underlying systemic immune dysfunction in ACLF, highlighting key pathophysiological pathways and their clinical significance. We provide an overview of ACLF including its global prevalence and clinical significance, against the background of the underlying immune dysfunction in its pathogenesis. The discussion focuses on innate immune alterations, such as impaired neutrophil and monocyte phagocytosis, excessive neutrophil extracellular trap (NET) formation, and monocyte/macrophage dysfunction contributing to immuneparesis and exaggerated inflammation, respectively, which evolve in an organ-specific manner. Dysregulation of natural killer (NK) cell cytotoxicity and adaptive immune dysfunction, including changes in T cell subpopulations and B cell antibody production in ACLF, are discussed. We further dissect the emerging evidence of molecular pathways driving dysfunction of immune cells and their impaired ability to control infections in ACLF, emphasizing the roles of pathogen- and damage-associated molecular patterns (PAMPs/DAMPs), toll-like receptor (TLR) signaling, oxidative stress, mitochondrial dysfunction, epigenetic/metabolic reprogramming and immune checkpoint molecules. The review expands on immune cell communication within the immune system (innate and adaptive), with other non-parenchymal and parenchymal cells and at the inter-organ level, detailing interactions between immune cells of key organs and compartments affected during ACLF, including the liver, circulation, brain, gut and kidney. Finally, we summarize the latest preclinical and clinical findings exploring biomarkers of immune dysfunction and immunomodulatory therapeutic strategies aimed at restoring immune homeostasis in patients with ACLF.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816233","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":"Beyond steroid-dependent care: can TNF blockade evolve into a precision therapy for autoimmune hepatitis?","authors":"Xinghuan Fu, Yan Wang, Guiqiang Wang","doi":"10.1016/j.jhep.2026.04.019","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.019","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816248","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":"Editorial:Professor Florence Wong - A career of scientific excellence, mentorship and lasting impact.","authors":"Zita Galvin","doi":"10.1016/j.jhep.2026.04.013","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.013","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816300","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":"Reply to Beyond binary classification of non-proportional hazards: methodological considerations for interpreting pivotal HCC trials.","authors":"Ezequiel Mauro, Amit Singal, Josep M Llovet","doi":"10.1016/j.jhep.2026.04.018","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.018","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816251","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":"IFRD1: a promising target in human liver regeneration.","authors":"Nicolas Lanthier, Peter Stärkel, Laurent Spahr","doi":"10.1016/j.jhep.2026.04.027","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.027","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816269","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":"Global biliary tract cancer genomics: from geographic patterns toward biological subtypes.","authors":"Anna Saborowski, Arndt Vogel","doi":"10.1016/j.jhep.2026.04.022","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.022","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816308","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":"Erratum to 'Hot and cold fibrosis: The role of serum biomarkers to assess immune mechanisms and ECM-cell interactions in human fibrosis' [J Hepatol 83 (2025) 239-257].","authors":"Andressa de Zawadzki, Diana J Leeming, Arun J Sanyal, Quentin M Anstee, Jörn M Schattenberg, Scott L Friedman, Detlef Schuppan, Morten A Karsdal","doi":"10.1016/j.jhep.2025.12.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.011","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773517","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":"Tim-3 facilitates dendritic cell ferroptosis and impairs anti-tumor immunity in steatohepatitis-related HCC.","authors":"Na Li, Xiaojia Song, Xueqi Peng, Mengzhen Li, Mengyao Zhu, Rong Xiao, Liwen Wang, Leyan Ling, Ying Zhao, Tixiao Wang, Zhiyuan Zhou, Zhuanchang Wu, Hua Tang, Lifen Gao, Xiaohong Liang, Chunyang Li, Chunhong Ma","doi":"10.1016/j.jhep.2026.04.010","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.04.010","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatocellular carcinoma (HCC) and confers resistance to immunotherapy. However, the underlying mechanisms remain unclear. We aimed to elucidate how the lipid-rich microenvironment of MASLD-HCC drives immune suppression and to identify actionable targets.</p><p><strong>Methods: </strong>DC-CD8⁺ T cell interaction in HCC tissues was analyzed by multiplexed immunofluorescence staining. Mechanistic studies employed high-fat diet (HFD)-induced MASLD-HCC mouse models, genetic or pharmacological inhibition of Tim-3, and DC depletion or adoptive transfer. Lipid peroxidation, ferroptosis, and immune interactions were assessed using flow cytometry, transcriptomics, and functional assays. Therapeutic efficacy of Tim-3 blockade, alone or combined with anti-PD-1 or lenvatinib was evaluated in preclinical models.</p><p><strong>Results: </strong>HFD reshapes the hepatic tumor immune microenvironment by inducing DC depletion and CD8⁺ T cell dysfunction, facilitating liver tumor progression. In human steatohepatitic-HCC, DC infiltration and DC-CD8⁺ T cell interactions were markedly impaired, and high DC-specific Tim-3 expression correlated with poor prognosis. Mechanistically, the lipid-rich microenvironment induced DC depletion via Tim-3-dependent lipid peroxidation and ferroptosis. Genetic or pharmacological inhibition of Tim-3 in DCs attenuated lipid peroxidation, restored DC survival and CD8⁺ T cell activation, and suppressed tumor growth. Moreover, Tim-3 blockade synergizes effectively with both anti-PD-1 and lenvatinib to achieve sustained tumor control.</p><p><strong>Conclusion: </strong>Our findings establish Tim-3 as a pivotal regulator of DC ferroptosis in metabolic liver cancer. Combining Tim-3 blockade with standard therapies represents a promising strategy to restore immune surveillance in metabolic-associated steatohepatitic HCC.</p><p><strong>Impact and implications: </strong>Our findings identify Tim-3 as a crucial metabolic immune checkpoint that governs DC ferroptosis and DC-mediated antitumor immunity in metabolic liver cancer. Targeted blockade of Tim-3 in DCs holds great therapeutic potential for the treatment of steatohepatitic HCC, particularly for patients with MASLD-HCC who exhibit resistance to anti-PD-1 therapy.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":33.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773510","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}