Hepatology最新文献

{"title":"Development and validation of pFIB scores for exclusion of significant liver fibrosis in pediatric MASLD.","authors":"Sander Lefere, Antonella Mosca, Christian Hudert, Ellen Dupont, Emer Fitzpatrick, Eirini Kyrana, Anil Dhawan, Laura Kalveram, Andrea Pietrobattista, Anja Geerts, Ruth De Bruyne","doi":"10.1097/HEP.0000000000001016","DOIUrl":"10.1097/HEP.0000000000001016","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking.</p><p><strong>Approach and results: </strong>Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe obesity, in whom liver fibrosis was evaluated by transient elastography. Logistic regression was performed to establish continuous (pFIB-c) and simplified (pFIB-6) diagnostic scores that accurately exclude significant (≥F2) fibrosis. Performance for each was compared to established noninvve fibrosis scores. These scores were validated in elastography (n=504) and multiple biopsy-proven MASLD (n=261) cohorts. Patient sex, ethnicity, weight z-score, homeostatic model assessment of insulin resistance index, ALT, and presence of hypertension were included in the scores. The pFIB-c and pFIB-6 exhibited good discriminatory capacity (c-statistic of 0.839 and 0.826), outperforming existing indices. Negative predictive values were >90% for both scores in the derivation and elastography validation cohorts. Performance in the histological cohorts varied (AUROCs for the pFIB-c between 0.710 and 0.770), as the scores were less accurate when applied to populations in tertiary referral centers characterized by a high prevalence of significant fibrosis and high ALT levels.</p><p><strong>Conclusions: </strong>Analyzing several cohorts totaling approximately 1100 children and adolescents, we developed novel risk scores incorporating readily available clinical variables. In accordance with the aim of excluding pediatric MASLD-associated fibrosis, the scores performed better in nonselected cohorts of children and adolescents living with obesity than in patients referred to tertiary liver units.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1276-1287"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726577","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":"Reversal of immune exhaustion for functional cure of chronic hepatitis B: Is the time right?","authors":"Arshi Khanam, Shyam Kottilil","doi":"10.1097/HEP.0000000000001059","DOIUrl":"10.1097/HEP.0000000000001059","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1129-1131"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981338","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":"Clinical decision support and electronic interventions to improve care quality in chronic liver diseases and cirrhosis.","authors":"Jin Ge, Valy Fontil, Sara Ackerman, Mark J Pletcher, Jennifer C Lai","doi":"10.1097/HEP.0000000000000583","DOIUrl":"10.1097/HEP.0000000000000583","url":null,"abstract":"<p><p>Significant quality gaps exist in the management of chronic liver diseases and cirrhosis. Clinical decision support systems-information-driven tools based in and launched from the electronic health record-are attractive and potentially scalable prospective interventions that could help standardize clinical care in hepatology. Yet, clinical decision support systems have had a mixed record in clinical medicine due to issues with interoperability and compatibility with clinical workflows. In this review, we discuss the conceptual origins of clinical decision support systems, existing applications in liver diseases, issues and challenges with implementation, and emerging strategies to improve their integration in hepatology care.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1353-1364"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058535","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}

{"title":"Letter to the Editor: Can pFIB scores reliably exclude significant liver fibrosis in pediatric MASLD?","authors":"Yusuf Yilmaz","doi":"10.1097/HEP.0000000000001068","DOIUrl":"10.1097/HEP.0000000000001068","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E115"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078548","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":"Letter to the Editor: Development and validation of pFIB scores for exclusion of significant liver fibrosis in pediatric MASLD.","authors":"Haowen Zhang, Xinyuan Zhu, Yunfeng Zhou, Yang Yuan","doi":"10.1097/HEP.0000000000001083","DOIUrl":"10.1097/HEP.0000000000001083","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E118"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138786","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 randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally suppressed patients with chronic hepatitis B who are HBeAg-negative.","authors":"Jiandan Qian, Yao Xie, Qianguo Mao, Qing Xie, Ye Gu, Xinyue Chen, Guoxin Hu, Yongfeng Yang, Jiajie Lu, Guizhou Zou, Qin Zhang, Lei Fu, Yongping Chen, Xiaolin Guo, Jinlin Hou, Yuemei Yan, Jinzi J Wu, Yimin Cui, Guiqiang Wang","doi":"10.1097/HEP.0000000000001006","DOIUrl":"10.1097/HEP.0000000000001006","url":null,"abstract":"<p><strong>Background and aims: </strong>Studies have shown that blocking the programmed cell death-1/programmed cell death ligand 1 pathway may lead to a potential cure for HBV infections. ASC22 (envafolimab) is a humanized, single-domain programmed cell death ligand 1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs.</p><p><strong>Approach and results: </strong>This randomized, single-blind, phase IIb trial enrolled patients with chronic hepatitis B in 2 cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22, and PBO, respectively. The mean changes in HBsAg from baseline at weeks 24 and 48 were -0.309 ( p < 0.001) and -0.272 ( p < 0.023) log 10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 ( p = 0.007) and -0.205 ( p = 0.12) log 10 IU/mL in the 2.5 mg/kg ASC22 group, and -0.003 and -0.063 log 10 IU/mL in the PBO group, respectively (intent-to-treat population). Three out of 10 patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most adverse events were mild (97.9%). There were no study drug-related serious adverse events in the 1.0 mg/kg ASC22 group.</p><p><strong>Conclusions: </strong>Subcutaneous administration of 1.0 mg/kg ASC22 once every 2 weeks for 24 weeks was shown to be safe and well-tolerated in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1328-1342"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557649","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":"Rethinking the roles of oncogenes: How does oncoprotein loss worsen liver carcinogenesis?","authors":"Angélique Gougelet","doi":"10.1097/HEP.0000000000001062","DOIUrl":"10.1097/HEP.0000000000001062","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1116-1119"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043806","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":"Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells.","authors":"Xudong Feng, Bing Feng, Jiahang Zhou, Jinfeng Yang, Qiaoling Pan, Jiong Yu, Dandan Shang, Lanjuan Li, Hongcui Cao","doi":"10.1097/HEP.0000000000000831","DOIUrl":"10.1097/HEP.0000000000000831","url":null,"abstract":"<p><strong>Background and aims: </strong>The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression.</p><p><strong>Approach and results: </strong>Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation. The treatment efficacy of MSCs can be attributed to decreased infiltration, activation, and pro-inflammatory cytokine production of intrahepatic B cells. Single-cell RNA sequencing revealed a distinct intrahepatic B cell atlas, and a subtype of naive B cells (B-II) was identified, which were markedly abundant in fibrotic liver, displaying mature features with elevated expression of several proliferative and inflammatory genes. Transcriptional profiling of total B cells revealed that intrahepatic B cells displayed activation, proliferation, and pro-inflammatory gene profile during LF. Fibrosis was attenuated in mice ablated with B cells (μMT) or in vivo treatment with anti-CD20. Moreover, fibrosis was recapitulated in μMT after adoptive transfer of B cells, which in turn could be rescued by MSC injection, validating the pathogenic function of B cells and the efficacy of MSCs on B cell-promoted LF progression. Mechanistically, MSCs could inhibit the proliferation and cytokine production of intrahepatic B cells through exosomes, regulating the Mitogen-activated protein kinase and Nuclear factor kappa B signaling pathways.</p><p><strong>Conclusions: </strong>Intrahepatic B cells serve as a target of MSCs, play an important role in the process of MSC-induced amelioration of LF, and may provide new clues for revealing the novel mechanisms of MSC action.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1211-1227"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11902620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140304197","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}

{"title":"Erratum: The Liver Meeting ® : San Diego, California, November 15-19, 2024.","authors":"","doi":"10.1097/HEP.0000000000001145","DOIUrl":"10.1097/HEP.0000000000001145","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E129-E130"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439702","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":"Epigenetic heterogeneity hotspots in human liver disease progression.","authors":"Ryan A Hlady, Xia Zhao, Louis Y El Khoury, Ryan T Wagner, Aesis Luna, Kien Pham, Nikolaos T Pyrosopoulos, Dhanpat Jain, Liguo Wang, Chen Liu, Keith D Robertson","doi":"10.1097/HEP.0000000000001023","DOIUrl":"10.1097/HEP.0000000000001023","url":null,"abstract":"<p><strong>Background and aims: </strong>Disruption of the epigenome is a hallmark of human disease, including liver cirrhosis and HCC. While genetic heterogeneity is an established effector of pathologic phenotypes, epigenetic heterogeneity is less well understood. Environmental exposures alter the liver-specific DNA methylation landscape and influence the onset of liver cancer. Given that currently available treatments are unable to target frequently mutated genes in HCC, there is an unmet need for novel therapeutics to prevent or reverse liver damage leading to hepatic tumorigenesis, which the epigenome may provide.</p><p><strong>Approach and results: </strong>We performed genome-wide profiling of DNA methylation, copy number, and gene expression from multiple liver regions from 31 patients with liver disease to examine their crosstalk and define the individual and combinatorial contributions of these processes to liver disease progression. We identified epigenetic heterogeneity hotspots that are conserved across patients. Elevated epigenetic heterogeneity is associated with increased gene expression heterogeneity. Cirrhotic regions comprise 2 distinct cohorts-one exclusively epigenetic, and the other where epigenetic and copy number variations collaborate. Epigenetic heterogeneity hotspots are enriched for genes central to liver function (eg, HNF1A ) and known tumor suppressors (eg, RASSF1A ). These hotspots encompass genes including ACSL1 , ACSL5 , MAT1A , and ELFN1 , which have phenotypic effects in functional screens, supporting their relevance to hepatocarcinogenesis. Moreover, epigenetic heterogeneity hotspots are linked to clinical measures of outcome.</p><p><strong>Conclusions: </strong>Substantial epigenetic heterogeneity arises early in liver disease development, targeting key pathways in the progression and initiation of both cirrhosis and HCC. Integration of epigenetic and transcriptional heterogeneity unveils putative epigenetic regulators of hepatocarcinogenesis.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1197-1210"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726578","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}