HepatologyPub Date : 2025-11-01Epub Date: 2025-02-18DOI: 10.1097/HEP.0000000000001273
Grace Lai-Hung Wong, Henry Lik-Yuen Chan
{"title":"Divergent trends in cirrhosis and liver cancer highlight the ongoing efforts required for hepatitis elimination.","authors":"Grace Lai-Hung Wong, Henry Lik-Yuen Chan","doi":"10.1097/HEP.0000000000001273","DOIUrl":"10.1097/HEP.0000000000001273","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1056-1057"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439692","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}
HepatologyPub Date : 2025-11-01Epub Date: 2025-03-05DOI: 10.1097/HEP.0000000000001289
Beat Moeckli, Charles-Henri Wassmer, Sofia El Hajji, Rohan Kumar, Joana Rodrigues Ribeiro, Parissa Tabrizian, Hao Feng, Gabriel Schnickel, Anand V Kulkarni, Manon Allaire, Sonal Asthana, Constantine J Karvellas, Glenda Meeberg, Lai Wei, Yasmina Chouik, Pramod Kumar, Robyn D Gartrell, Mercedes Martinez, Elise Kang, Miguel Sogbe, Bruno Sangro, Birgit Schwacha-Eipper, Andreas Schmiderer, Felix J Krendl, Nicolas Goossens, Stephanie Lacotte, Philippe Compagnon, Christian Toso
{"title":"Determining safe washout period for immune checkpoint inhibitors prior to liver transplantation: An international retrospective cohort study.","authors":"Beat Moeckli, Charles-Henri Wassmer, Sofia El Hajji, Rohan Kumar, Joana Rodrigues Ribeiro, Parissa Tabrizian, Hao Feng, Gabriel Schnickel, Anand V Kulkarni, Manon Allaire, Sonal Asthana, Constantine J Karvellas, Glenda Meeberg, Lai Wei, Yasmina Chouik, Pramod Kumar, Robyn D Gartrell, Mercedes Martinez, Elise Kang, Miguel Sogbe, Bruno Sangro, Birgit Schwacha-Eipper, Andreas Schmiderer, Felix J Krendl, Nicolas Goossens, Stephanie Lacotte, Philippe Compagnon, Christian Toso","doi":"10.1097/HEP.0000000000001289","DOIUrl":"10.1097/HEP.0000000000001289","url":null,"abstract":"<p><strong>Background and aims: </strong>Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced HCC patients awaiting liver transplantation (LT). However, concerns about the risk of posttransplant rejection persist.</p><p><strong>Approach and results: </strong>We conducted an international retrospective cohort study including 119 HCC patients who received ICIs prior to LT. We analyzed the incidence of allograft rejection, graft loss, and posttransplant recurrence with a particular focus on the washout period between the last ICI dose and LT. In this study, 24 of the 119 (20.2%) patients experienced allograft rejection with a median time to rejection of 9 days (IQR 6-10) post-LT. A linear relationship was observed between shorter washout periods and higher rejection risk. Washout periods <30 days (OR: 21.3, 95% CI: 5.93-103, p< 0.001) and between 30 and 50 days (OR: 9.48, 95% CI 2.47-46.8, p =0.002) were significantly associated with higher rejection rates in the univariate analysis compared to the washout period above 50 days. Graft loss as a result of rejection occurred in 6 patients (25%) with rejection. No factors related to grafts were associated with rejection. A longer washout period was not associated with a lower recurrence-free survival posttransplantation at 36 months (71% vs. 67%, p =0.71).</p><p><strong>Conclusions: </strong>Our findings suggest that a washout period longer than 50 days for ICIs before LT appears to be safe with respect to rejection risk. While these results may help guide clinical decision-making, future prospective studies are essential to establish definitive guidelines.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1122-1137"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555468","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}
HepatologyPub Date : 2025-11-01Epub Date: 2024-07-17DOI: 10.1097/HEP.0000000000001010
{"title":"Diagnosis and Management of Hepatocellular Carcinoma.","authors":"","doi":"10.1097/HEP.0000000000001010","DOIUrl":"10.1097/HEP.0000000000001010","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E117-E120"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632151","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}
HepatologyPub Date : 2025-11-01Epub Date: 2024-01-24DOI: 10.1097/HEP.0000000000000760
H Catherine Wilbur, Heloisa P Soares, Nilofer S Azad
{"title":"Neoadjuvant and adjuvant therapy for biliary tract cancer: Advances and limitations.","authors":"H Catherine Wilbur, Heloisa P Soares, Nilofer S Azad","doi":"10.1097/HEP.0000000000000760","DOIUrl":"10.1097/HEP.0000000000000760","url":null,"abstract":"<p><p>Biliary tract cancers (BTC) are a rare and aggressive consortium of malignancies, consisting of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma. While most patients present with metastatic disease, a minority of patients with BTC are eligible for curative surgical resection at the time of presentation. However, these patients have poor 5-year overall survival rates and high rates of recurrence, necessitating the improvement of the neoadjuvant and adjuvant treatment of BTC. In this review, we assess the neoadjuvant and adjuvant clinical trials for the treatment of BTC and discuss the challenges and limitations of clinical trials, as well as future directions for the treatment of BTC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1287-1302"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544887","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}
HepatologyPub Date : 2025-11-01Epub Date: 2024-03-19DOI: 10.1097/HEP.0000000000000860
Mazen Noureddin
{"title":"MASH clinical trials and drugs pipeline: An impending tsunami.","authors":"Mazen Noureddin","doi":"10.1097/HEP.0000000000000860","DOIUrl":"10.1097/HEP.0000000000000860","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease, formerly known as NAFLD, has ascended to prominence as the predominant chronic liver disease in Western countries and now stands as a leading cause of liver transplantations. In the more advanced stage, metabolic dysfunction-associated steatohepatitis (MASH) may lead to fibrosis, a gateway to cirrhosis, liver cancer, and liver failure. Despite extensive research and exploration of various drug mechanisms, the anticipation for the inaugural approved drug to materialize by 2024 is palpable, marking a significant milestone. Numerous pathways have been investigated for MASH treatment, exploring thyroid hormone receptors, glucagon-like peptides 1, peroxisome proliferator-activated receptors, and agents influencing hepatic steatosis synthesis, inflammatory pathways, genetic components, fibrosis mechanisms, and an array of other avenues. Over time, key regulatory directions have crystallized, now manifesting in 2 primary endpoints under investigation: resolution of steatohepatitis without worsening fibrosis and/or improvement of fibrosis stage without worsening of steatohepatitis, especially used in phase 3 clinical trials, while alternative noninvasive endpoints are explored in phase 2 trials. The prospect of proving efficacy in clinical trials opens doors to combination therapies, evaluating the ideal combination of drugs to yield comprehensive benefits, extending beyond the liver to other organs. Certain combination drug trials are already underway. In this review, we discuss the forefront of MASH drug research as of 2023/2024, illuminating mechanisms, outcomes, and future trajectories. Furthermore, we tackle the challenges confronting MASH trials and propose potential strategies for surmounting them.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1325-1340"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178757","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}
HepatologyPub Date : 2025-11-01Epub Date: 2025-04-08DOI: 10.1097/HEP.0000000000001349
Xinxing Tantai, Lu Li, Shejiao Dai
{"title":"Letter to the Editor: Post-TIPS hemodynamic target adherence fails to improve outcomes in cirrhotic patients.","authors":"Xinxing Tantai, Lu Li, Shejiao Dai","doi":"10.1097/HEP.0000000000001349","DOIUrl":"10.1097/HEP.0000000000001349","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E124-E125"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810130","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}
HepatologyPub Date : 2025-11-01Epub Date: 2024-02-13DOI: 10.1097/HEP.0000000000000786
Xiaobo Wang, Liang Zhang, Bingning Dong
{"title":"Molecular mechanisms in MASLD/MASH-related HCC.","authors":"Xiaobo Wang, Liang Zhang, Bingning Dong","doi":"10.1097/HEP.0000000000000786","DOIUrl":"10.1097/HEP.0000000000000786","url":null,"abstract":"<p><p>Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such as genetic mutations, carcinogen exposure, immune microenvironment, and microbiome. MASH-HCC exhibits distinct molecular and immune characteristics compared to other causes of HCC and affects both men and women equally. The management of early to intermediate-stage MASH-HCC typically involves surgery and locoregional therapies, while advanced HCC is treated with systemic therapies, including anti-angiogenic therapies and immune checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings while also providing the most current insights into the intricate molecular processes underlying MASH-HCC development. We delve into MASH-HCC-associated genetic variations and somatic mutations, disease progression and research models, multiomics analysis, immunological and microenvironmental impacts, and discuss targeted/combined therapies to overcome immune evasion and the biomarkers to recognize treatment responders. By furthering our comprehension of the molecular mechanisms underlying MASH-HCC, our goal is to catalyze the advancement of more potent treatment strategies, ultimately leading to enhanced patient outcomes.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1303-1324"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HepatologyPub Date : 2025-11-01Epub Date: 2025-01-03DOI: 10.1097/HEP.0000000000001216
Kimberly P Newton, Dulshan Jayasekera, Amanda L Blackford, Cynthia Behling, Laura A Wilson, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Miriam B Vos, Jeffrey B Schwimmer
{"title":"Longitudinal response to standard of care in pediatric metabolic dysfunction-associated steatotic liver disease: Rates of improvement and worsening, and factors associated with outcomes.","authors":"Kimberly P Newton, Dulshan Jayasekera, Amanda L Blackford, Cynthia Behling, Laura A Wilson, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Miriam B Vos, Jeffrey B Schwimmer","doi":"10.1097/HEP.0000000000001216","DOIUrl":"10.1097/HEP.0000000000001216","url":null,"abstract":"<p><strong>Background and aims: </strong>Longitudinal outcomes in children with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear due to the absence of a standardized monitoring approach. This study aimed to (1) define improvement and worsening in children with MASLD, (2) estimate rates of improvement or deterioration with the standard of care (SOC) over 1 and 2 years, and (3) identify baseline and longitudinal factors associated with improvement or worsening.</p><p><strong>Approach and results: </strong>Using data from 2 large randomized controlled trials, we derived definitions for composite improvement and worsening of MASLD based on associations between changes in ALT, GGT, and liver histology after 1 and 2 years. Improvement was defined as ≥40% decrease in ALT and ≥20% decrease in GGT and worsening as ≥20% increase in both ALT and GGT. We applied definitions to a cohort of 440 children with MASLD. After 1 year of SOC, 22% of children with MASLD showed improvement, increasing to 31% after 2 years. However, 20% showed worsening after both 1 and 2 years despite receiving SOC. Logistic regression analysis, employing stepwise model selection, identified changes in body mass index z-score and cholesterol to be most associated with improvement or deterioration.</p><p><strong>Conclusions: </strong>This study developed criteria for improvement and worsening in children with MASLD over 1 and 2 years of follow-up. With SOC, over one-quarter of children are likely to improve while one-fifth of children are likely to worsen. Targeting interventions that affect body mass index and lipid parameters may help improve MASLD over time.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1198-1210"},"PeriodicalIF":15.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}