Journal of Hepatology最新文献

{"title":"EASL Clinical Practice Guidelines on the management of extrahepatic cholangiocarcinoma","authors":"","doi":"10.1016/j.jhep.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.03.007","url":null,"abstract":"Recent years have witnessed significant advances in the imaging, molecular profiling, and systemic treatment of cholangiocarcinoma (CCA). Despite this progress, the early detection, precise classification, and effective management of CCA remain challenging. Owing to recent developments and the significant differences in CCA subtypes, EASL commissioned a panel of experts to draft evidence-based recommendations on the management of extrahepatic CCA, comprising distal and perihilar CCA. Particular attention is given to the need for accurate classification systems, the integration of emerging molecular insights, and practical strategies for diagnosis and treatment that reflect real-world clinical scenarios.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"27 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931080","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":"EASL Clinical Practice Guidelines on the management of autoimmune hepatitis","authors":"","doi":"10.1016/j.jhep.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.03.017","url":null,"abstract":"Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology which may affect any patient irrespective of age, sex, and ethnicity. At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis. The aim of these EASL guidelines is to provide updated guidance on the diagnosis and management of AIH both in adults and children. Updated guidance on the management of patients with variants and specific forms of AIH is also provided, as is detailed guidance on the management of AIH-associated cirrhosis, including surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"39 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931296","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":"EASL Clinical Practice Guidelines on extrahepatic abdominal surgery in patients with cirrhosis and advanced chronic liver disease","authors":"","doi":"10.1016/j.jhep.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.008","url":null,"abstract":"Extrahepatic surgery in patients with cirrhosis of the liver represents a growing clinical challenge due to the increasing prevalence of chronic liver disease and improved long-term survival of these patients. The presence of cirrhosis significantly increases the risk of perioperative morbidity and mortality following abdominal surgery. Advances in preoperative risk stratification, surgical techniques, and perioperative care have led to better outcomes, yet integration of these improvements into routine clinical practice is needed. These clinical practice guidelines provide comprehensive recommendations for the assessment and perioperative management of patients with cirrhosis undergoing extrahepatic surgery. An individualised patient-centred risk assessment by a multidisciplinary team including hepatologists, surgeons, anaesthesiologists, and other support teams is essential.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"109 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931081","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":"EASL Clinical Practice Guidelines on the management of hepatitis B virus infection","authors":"","doi":"10.1016/j.jhep.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.03.018","url":null,"abstract":"The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"35 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931082","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":"Safety and efficacy of elafibranor in primary sclerosing cholangitis: The ELMWOOD phase II randomized-controlled trial","authors":"Cynthia Levy, George F. Abouda, Bahri M. Bilir, Alan Bonder, Christopher L. Bowlus, Isabel Campos-Varela, Nora Cazzagon, Natasha Chandok, Kuldeep Cheent, Helena Cortez-Pinto, Münevver Demir, Michael T. Dill, Bertus Eksteen, Jonathan M. Fenkel, Richard Gilroy, Hin Hin Ko, Ira M. Jacobson, Yiannis Kallis, Marcelo Kugelmas, Velimir Luketic, Kris V. Kowdley","doi":"10.1016/j.jhep.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.025","url":null,"abstract":"<h3>Background &amp; Aims</h3>Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease. Elafibranor, a dual peroxisome proliferator-activated receptor-α/δ agonist, was investigated in the phase II ELMWOOD trial (NCT05627362).<h3>Methods</h3>This 12-week, double-blind trial enrolled adults with PSC and alkaline phosphatase (ALP) ≥1.5× the upper limit of normal. The primary endpoint was elafibranor safety <em>vs</em>. placebo. Additional endpoints included relative mean change from baseline in ALP and enhanced liver fibrosis (ELF) score.<h3>Results</h3>A total of 68 participants (male: 54.4%; mean age: 46.3 years; inflammatory bowel disease: 55.9%) were randomized to elafibranor 80 mg (n = 22), elafibranor 120 mg (n = 23), or placebo (n = 23). At baseline, 70.6% were on ursodeoxycholic acid, 48.5% had ELF scores &gt;9.8, and the mean ALP level was 369.5 U/L. At Week 12, rates of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation in participants on elafibranor 80 mg, 120 mg, and placebo were 68.2%, 78.3%, and 69.6%, and 4.5%, 4.3%, and 8.7%, respectively. Serious TEAEs occurred only in participants on placebo (4.3%). Participants on elafibranor 80 mg and 120 mg had reductions in ALP <em>vs.</em> placebo (least squares mean treatment difference [95% CI]: −35.3% [−49.2, −21.4] and −54.7% [−68.3, −41.0], respectively). ALP normalization occurred only in participants on elafibranor 80 mg (9.1%) and 120 mg (17.4%). The LS mean treatment differences (95% CI) in change from baseline in ELF scores in participants on elafibranor 80 mg and 120 mg <em>vs.</em> placebo were –0.19 (−0.52, +0.15) and –0.28 (−0.62, +0.06), respectively.<h3>Conclusions</h3>Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo. A greater magnitude of response was observed with elafibranor 120 mg compared with 80 mg.<h3>Impact and implications</h3>For people with primary sclerosing cholangitis (PSC), there is a need for a well-tolerated and effective treatment that will enhance quality of life, prevent disease progression, and improve long-term outcomes. Here, we present results from the double-blind period of the phase II ELMWOOD trial in PSC, wherein elafibranor, a peroxisome proliferator-activated receptor-α/δ agonist, demonstrated a favorable safety profile, provided greater biochemical improvements over 12 weeks compared with placebo, and appeared to stabilize markers of fibrosis and improve pruritus. These findings support larger and longer term investigations of elafibranor to explore its therapeutic potential as a treatment for people with PSC.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"35 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931168","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":"Overcoming drug resistance by harnessing mitochondrial divisome for treating cholangiocarcinoma","authors":"Mengwei Niu, Wen-Xing Ding","doi":"10.1016/j.jhep.2025.04.038","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.038","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Competing interests</h2>The authors declare no conflicts of interest that pertain to this work.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section><section><section><h2>Authors’ contributions</h2>M.W &amp; WXD conceived and wrote the manuscript.</section></section><section><section><h2>Data Availability Statement:</h2>There are no data associated with this study.</section></section><section><section><h2>Financial support</h2>This study was supported in part by the National Institute of Health (NIH) funds R37 AA020518, R21 AA030617 and R01AA031230 (WXD).</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"76 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931300","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":"Carvedilol is superior to propranolol in preventing first and further decompensation, and mortality in patients with cirrhosis","authors":"Maria Christaki, Dimitrios Biros, Ilias Tsiakas, Haralampos Milionis, Georgios N. Kalambokis","doi":"10.1016/j.jhep.2025.04.032","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.032","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>MC, DB, IT and HM participated in the design of the study and contributed to the concept of the letter. GK interpreted the data and drafted the manuscript. All authors critically revised the manuscript and approved its final draft.</section></section><section><section><h2>Data availability statement</h2>Data are available on reasonable request.All authors confirm that we did not and will not submit the data included in the letter as original publication elsewhere.</section></section><section><section><h2>Financial support</h2>The authors received no financial support to produce this manuscript.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors declare no conflicts of interest that pertain to this work.<ul><li><span></span><span>Please refer to the accompanying ICMJE disclosure forms for further details.</span></li></ul></section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"96 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920308","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":"Decoding the Resistin-CAP1 Pathway in Intermediate Monocytes Mediating Liver Allograft Rejection","authors":"Peijun Yang, Xudan Wang, Weikang Wu, Juzheng Yuan, Xinrui Wang, Rui Ding, Weiwei Cao, Cong Li, Yinjie Wang, Zihan Xi, Kefeng Dou, Xiao Li, Kaishan Tao","doi":"10.1016/j.jhep.2025.04.037","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.037","url":null,"abstract":"<h3>Background &amp; Aims</h3>Lymphocytes are widely recognized as the primary mediators of cellular rejection post-liver transplantation. However, conventional immunosuppressive regimens that target lymphocytes, such as calcineurin phosphatase inhibitors, corticosteroids, or lymphocyte-depleting antibodies, can only partially mitigate rejection while inducing severe adverse effects. This necessitates the search for novel immunotherapeutic targets.<h3>Methods</h3>We harnessed the power of single-cell RNA sequencing and spatial transcriptome in 24 rat transplanted liver and peripheral blood single nucleated cells (PBMCs) samples to derive gene expression signatures recapitulating 13 cell phenotypes. We used flow cytometry, multifactor assays and multiple recombinant assays to validate <em>in vitro</em> and <em>in vivo</em> the role of the target protein Resistin on human T-cell function, as well as the Resistin-CAP1 interaction. Gold nanoparticles were used to package <em>Retn</em> siRNA sequences to validate the role of <em>Retn</em> knockdown on acute rejection after liver transplantation.<h3>Results</h3>By distinguishing between donor and recipient cells, we delineate the dynamic landscape of immune cells during allograft rejection and their spatial distributions across donors and recipients. Our findings underscore the pivotal role of recipient derived intermediate monocytes in cellular rejection. Using CellChat ligand-receptor analysis, we identify the Resistin-CAP1 pathway as a key mechanism by which intermediate monocytes participate in T cell-mediated rejection reactions. We confirm that Resistin knockdown significantly alleviates acute rejection after rat liver transplantation, markedly extending the survival of recipients using innovative nanogold technology.<h3>Conclusion</h3>These findings offer insights into the dynamic changes in the alloimmune microenvironment, pinpointing intermediate monocytes as potential diagnostic and immunotherapeutic targets during allograft rejection. This study holds significant importance in advancing non-invasive diagnostic technologies and immunotherapeutic strategies for allogeneic rejection.<h3>Impact and implications</h3>This study pioneers the application of spatial transcriptomics in liver transplantation, providing a comprehensive analysis of immune cell spatial distribution, complemented by Souporcell-based chimerism assessment. We demonstrate that intermediate monocytes play a pivotal role in T cell-mediated acute rejection via the Resistin-CAP1 signaling axis. Targeting this pathway using nanogold-siRNA technology effectively mitigates rejection and enhances graft survival. These findings contribute novel insights into the mechanisms of transplant rejection and present promising avenues for the development of targeted therapeutic and diagnostic strategies in liver transplantation.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"25 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920307","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":"High inherited risk predicts age-associated increases in fibrosis in patients with MASLD","authors":"Luis Antonio Díaz, William Alazawi, Saaket Agrawal, Juan Pablo Arab, Marco Arrese, Francisco Idalsoaga, Fernando Javier Barreyro, Adrian Gadano, Sebastián Marciano, Jorge Martínez Morales, Cristiane Villela-Nogueira, Nathalie Leite, Claudia Alves Couto, Rafael Theodoro, Mísia Joyner de Sousa Dias Monteiro, Claudia P. Oliveira, Mario G. Pessoa, Mario Reis Alvares-da-Silva, Egbert Madamba, Ricki Bettencourt, Veeral Ajmera","doi":"10.1016/j.jhep.2025.04.035","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.035","url":null,"abstract":"<h3>Background &amp; Aims</h3>Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD.<h3>Methods</h3>This cross-sectional study included prospectively recruited adults with MASLD aged 18–70 who underwent magnetic resonance elastography (MRE) and genotyping for <em>PNPLA3, TM6SF2, MBOAT7, GCKR,</em> and <em>HSD17B13</em>. A genetic risk score (GRS) was calculated as the sum of established risk alleles in <em>PNPLA3</em> minus protective variants in <em>HSD17B13</em> (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America.<h3>Results</h3>Among 570 participants, the median age was 57 [49–64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1–3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12–0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. <em>PNPLA3</em> genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02–0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52–1.22, p&lt;0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population.<h3>Conclusion</h3>GRS, PRS-HFC, PRS-5, and <em>PNPLA3</em> genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring.<h3>IMPACT AND IMPLICATIONS</h3>This study provides granular evidence that genetic predisposition, particularly the <em>PNPLA3</em> G/G genotype, significantly influences the trajectory of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), with a more pronounced impact emerging after the fourth decade of life. These findings highlight the importance of incorporating genetic risk assessment into MASLD management, as it allows for the early identification of high-risk individuals who may benefit from more frequent monitoring and targeted interventions. Given the rising global burden of MASLD, clinicians, researchers, and policymakers should consider integrating genetic stratification into existing risk assessment frameworks to refine screening and surveillance strategies. By optimizing patient selection for non-invasive fibrosis assessment and potential therapeutic interventions, this approach could enhance precision medicine efforts and may improve long-term outcomes.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"21 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910656","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":"Does the UK DCD Risk Score have statistical flaws?","authors":"Simon Schwab, Vanessa Banz, Ulrike Held, Linard Hoessly, Giulia Magini","doi":"10.1016/j.jhep.2025.04.030","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.04.030","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>SS drafted the manuscript and performed the analysis. All authors revised, reviewed, and approved the final manuscript.</section></section><section><section><h2>Financial support</h2>The authors received no financial support to produce this letter.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors declare no conflicts of interest associated with this letter.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"46 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905718","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}