Hepatology最新文献

{"title":"Altered blood-brain barrier permeability is associated with abnormal distant connectivity and regional homogeneity in covert hepatic encephalopathy - a cross sectional study.","authors":"Joga Chaganti,Georgia Zeng,Adwaita Patil,Ian Lockart,Michelle Dellalana,Sara Montagnese,Bruce Brew,Mark Danta","doi":"10.1097/hep.0000000000001343","DOIUrl":"https://doi.org/10.1097/hep.0000000000001343","url":null,"abstract":"BACKGROUNDCovert hepatic encephalopathy (CHE) is clinically underrecognized. Using MRI, we explored the relationship between functional connectivity as a marker of executive dysfunction and the blood-brain barrier permeability marker KTRANS in a cross-sectional cohort of covert HE (CHE), no HE (NHE), and healthy controls (HC).METHODSThis study was a single-center prospective cohort study conducted between 2018 and 2021. CHE was diagnosed using the Psychometric Hepatic Encephalopathy Score (PHES) with an abnormality threshold of <-4. Blood brain barrier permeability was determined using MRI KTRANS, based on cerebral efflux of gadolinium from blood plasma to the extravascular space. Resting-state fMRI determined the intrinsic dynamics of regions of the brain.RESULTSThree cohorts were recruited: cirrhosis and CHE (n=17); cirrhosis with no HE (NHE; n=13); and healthy controls (n=10). There was a significant negative correlation (r=-0.59, p=0.003) between KTRANS and components of the Default Mode Network (DMN). Group-level ANOVA (F-test) revealed a significant difference between groups in functional connectivity within the Salience Network (SN) (Cluster level significance, F(4,62)=8.45, pcorrected=0.000005) and the DMN (Cluster level significance, F(4,62)=6.20, pcorrected=0.0004). The analysis revealed significant differences in regional homogeneity between the CHE and Health Controls.CONCLUSIONThere was a strong association between disrupted blood-brain barrier (BBB) integrity and attenuated functional connectivity, with reductions in functional connectivity within the DMN and Frontoparietal Network (FPN), circuits closely linked to executive control. This attenuation was evident both in local regional and in distant connectivity within these networks.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"224 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897358","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: Antibody-mediated rejection in liver transplantation following immune checkpoint inhibitors treatment.","authors":"Pusen Wang,Lin Zhong","doi":"10.1097/hep.0000000000001373","DOIUrl":"https://doi.org/10.1097/hep.0000000000001373","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"24 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897465","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: Redefining post-resection care: Critical analysis of adjuvant TACE in curative hepatocellular carcinoma management.","authors":"Qianqian Zhang,Quanmao Song,Yanna Liu,Jinpeng Li","doi":"10.1097/hep.0000000000001327","DOIUrl":"https://doi.org/10.1097/hep.0000000000001327","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"90 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897457","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: Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content.","authors":"Manuel Romero-Gómez,Eric Lawitz","doi":"10.1097/hep.0000000000001372","DOIUrl":"https://doi.org/10.1097/hep.0000000000001372","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"71 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897464","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":"Organ damage proteomic signature identifies patients with MASLD at-risk of systemic complications","authors":"Carlos José Pirola, Luis Diambra, Tomas Fernández Gianotti, Gustavo Osvaldo Castaño, Julio San Martino, Martin Garaycoechea, Silvia Sookoian","doi":"10.1097/hep.0000000000001346","DOIUrl":"https://doi.org/10.1097/hep.0000000000001346","url":null,"abstract":"Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world’s population and is associated with multisystemic comorbidities. We combined multidimensional OMICs approaches to explore the feasibility of using high-throughput targeted circulating proteomics to track systemic organ damage and infer the underlying molecular mechanisms. Methods: We evaluated a 92-plex panel of prioritized proteins with pathophysiological relevance to organ damage in serum samples of patients using in-depth phenotyping. We included proteomic data from 60,042 individuals in the discovery and replication stages using diverse study designs and cross-proteomic platforms. We used deconvolution strategies to investigate whether the affected liver participated in the expression of biomarkers of organ damage. To assess cell type-specific transcriptional changes in the selected target, we used liver organoid data. Findings: The implicated proteins, including ADGRG1 (GPR56), are deregulated in patients who are at-risk of progressive disease and significant fibrosis. ADGRG1 was validated as a surrogate for organ damage, as it was associated with increased risk of end-stage liver disease, moderate but clinically significant risk of death, chronic obstructive pulmonary disease and ischaemic heart disease over a 16-year follow-up, regardless of the subject’s MASLD status. ADGRG1 liver expression mirrors the circulation pattern. Mechanistic insights show that ADGRG1 shifts its transcriptional profile from low expression to upregulation in cells of the fibrotic and inflammatory niche in response to injury. Conclusions: Our study provides a framework for potential mechanisms associated with systemic diseases that facilitates holistic management by stratifying patients with MASLD into subclasses at-risk of extrahepatic manifestations.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"111 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897538","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":"Alcohol-induced disruption of hepatic m6A modification exacerbates alcohol-associated steatohepatitis by impairing liver immune microenvironment homeostasis.","authors":"Jinghao Yao,Pei Liu,Xinkun Teng,Dejie Kong,Biwei Han,Chengying Cui,Mingwei Yin,Xinze Yan,Ang Zhao,Yingquan Ye,Haiyuan Shen,Miaomiao Wu,Juan Wang,Qianying Cheng,Xiaoli Wei,Yushun Wang,Quan Yuan,Yang Li,Hua Wang","doi":"10.1097/hep.0000000000001374","DOIUrl":"https://doi.org/10.1097/hep.0000000000001374","url":null,"abstract":"BACKGROUND AND AIMSAlcohol-associated steatohepatitis (ASH), a severe form of alcohol-associated liver disease (ALD), is characterized by pronounced steatosis and immune cells infiltration. As an inflammatory disease, ASH still lacks effective immunotherapies, and the mechanisms underlying alcohol-induced immune imbalance in the liver microenvironment remain elusive. RNA modifications are known to maintain hepatic homeostasis during physiological and pathological processes. This study aimed to investigate the alteration of RNA modification in ASH and its specific roles in regulating immune homeostasis.APPROACH AND RESULTSIn this study, we found that the levels of RNA N6-methyladenosine (m6A) modification and its key writer, METTL3, are markedly reduced in mice livers during ASH. Notably, hepatocyte-specific Mettl3 knockout exacerbated ASH by enhancing steatosis and neutrophil infiltration, whereas hepatocyte-specific Mettl3 overexpression alleviated these effects. Mechanistically, ethanol promotes METTL3 degradation via E3-ubiquitin-ligase STUB1-mediated ubiquitination and disrupts the protective interaction between HSP70 and METTL3, impairing hepatic m6A modification. Furthermore, the expression of ATF3 was upregulated via m6A-dependent mechanism. Importantly, hepatocyte-specific Atf3 overexpression abolished METTL3-mediated amelioration of ASH, whereas hepatocyte-specific Atf3 knockdown attenuated Metl3 knockout-induced exacerbation of ASH in vivo. Consistently, high hepatic ATF3 expression is associated with an inflammatory liver microenvironment in ALD patients.CONCLUSIONSCollectively, our results demonstrate that alcohol consumption disrupts the homeostasis of hepatic immune microenvironment in ASH through impairment of METTL3-dependent m6A RNA modification. Targeting METTL3 to preserve its enzymatic activity and stability could represent a novel therapeutic avenue for ASH intervention.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"104 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893412","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: Oversights in Stratification and Viral Screening— A Critical Appraisal of a MetS–Cholangiocarcinoma Cohort","authors":"Mei-Hsuan Lee","doi":"10.1097/hep.0000000000001370","DOIUrl":"https://doi.org/10.1097/hep.0000000000001370","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"19 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889659","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: Oversights in stratification and viral screening— A critical appraisal of a MetS–cholangiocarcinoma cohort","authors":"Jian Huang","doi":"10.1097/hep.0000000000001369","DOIUrl":"https://doi.org/10.1097/hep.0000000000001369","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"104 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889662","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":"AASLD Practice Statement on the evaluation and management of metabolic dysfunction-associated steatotic liver disease in children","authors":"Stavra A. Xanthakos, Samar Ibrahim, Kathryn Adams, Rohit Kohli, Pushpa Sathya, Shikha Sundaram, Miram Vos, Ashish Dhawan, Sonia Caprio, Cindy Behling, Jeffrey B. Schwimmer","doi":"10.1097/hep.0000000000001368","DOIUrl":"https://doi.org/10.1097/hep.0000000000001368","url":null,"abstract":"Given the high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in children and its distinct epidemiological, clinical, and histopathological differences from adult disease, the American Association for the Study of Liver Diseases (AASLD) commissioned this pediatric-focused evidence-based practice statement. A multidisciplinary writing group—encompassing expertise in pediatric hepatology, gastroenterology, endocrinology, and liver pathology—conducted a comprehensive PubMed literature search for studies published through March 6, 2024, involving pediatric participants (ages 0–18 y) with NAFLD or MASLD. The review addressed epidemiology, pathophysiology, natural history, screening, diagnosis, treatment, comorbidity management, outcome monitoring, and transition of care. Using the highest available level of evidence—randomized controlled trials, large observational cohort studies, systematic reviews, and meta-analyses—30 evidence-guided practice statements were developed. Where high-quality evidence was lacking, expert consensus was employed, and critical knowledge gaps were identified to inform future research priorities. This document highlights key concepts relevant to pediatric MASLD, especially regarding diagnostic criteria, noninvasive assessment tools, and therapeutic approaches. It also discusses the implications of the 2023 nomenclature revision, which emphasizes evaluating both hepatic steatosis and cardiometabolic risk factors. With increasing recognition of MASLD’s cardiometabolic burden and long-term health consequences, this practice statement provides a structured framework to advance clinical care and research in pediatric MASLD.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"86 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889663","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":"Moving beyond the liver – proteomics as a molecular footprint of systemic damage in metabolic dysfunction-associated steatotic liver disease","authors":"Mary E. Rinella","doi":"10.1097/hep.0000000000001376","DOIUrl":"https://doi.org/10.1097/hep.0000000000001376","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"58 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889664","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}