HepatologyPub Date : 2026-09-24DOI: 10.1097/hep.0000000000001846
Xianhua Mao, Hong Fan, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen
{"title":"Erratum: GLP-1 receptor agonist–SGLT-2 inhibitor combination and risk of major adverse liver and cardiovascular outcomes in adults with MASLD and type 2 diabetes","authors":"Xianhua Mao, Hong Fan, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H. Nguyen","doi":"10.1097/hep.0000000000001846","DOIUrl":"https://doi.org/10.1097/hep.0000000000001846","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027534","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 : 2026-09-24DOI: 10.1097/hep.0000000000001870
Anabel Fernández-Iglesias, Edward N. Harris, Nidhi Jalan-Sakrikar, Savneet Kaur, Bartlomiej Zapotoczny, Kenichi Ikejima, Jordi Gracia-Sancho
{"title":"The hepatic sinusoid as a regulatory niche: From cellular specialization to precision hepatology","authors":"Anabel Fernández-Iglesias, Edward N. Harris, Nidhi Jalan-Sakrikar, Savneet Kaur, Bartlomiej Zapotoczny, Kenichi Ikejima, Jordi Gracia-Sancho","doi":"10.1097/hep.0000000000001870","DOIUrl":"https://doi.org/10.1097/hep.0000000000001870","url":null,"abstract":"The hepatic sinusoid is increasingly recognized as a multicellular, spatially organized and therapeutically actionable regulatory niche rather than merely a specialized microvascular bed. Liver sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells, recruited leukocytes, lymphocytes, cholangiocytes, hepatocytes and extracellular matrix components form dynamic networks that coordinate vascular exchange, immune surveillance, metabolic zonation, tissue repair and systemic communication. Recent advances in single-cell and spatial omics, quantitative imaging, mechanobiology and human tissue models have revealed how endothelial dedifferentiation, macrophage and T-cell programming, stellate cell plasticity, extracellular matrix remodeling and stromal control of cancer immunity interact across disease stages. These insights recast fibrosis, portal hypertension, metabolic dysfunction-associated steatotic liver disease and liver cancer as disorders of sinusoidal communication and niche organization, while linking sinusoidal dysfunction to aging and extrahepatic axes. In this review, we trace the evolution of sinusoidal research from cellular specialization to integrated niche biology, focusing on the next unresolved layer: which cell-cell interactions are causal, how they change with disease stage and how they can be measured or perturbed in human tissue. We define priorities for mapping disease-stage-specific human niches, restoring protective functions, developing composite biomarkers and standardizing translational platforms. The hepatic sinusoid is considered here as a tissue-level regulatory unit whose failure can be interrogated through coupled vascular, stromal, immune, metabolic and mechanical readouts.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"98 8 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027538","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 : 2026-09-18DOI: 10.1097/hep.0000000000001864
Shangqing Yang, Firat Nebioglu, Minh Tu Pham, Yen-Chia Lin, Andreas Pichlmair, Shirin Nkongolo, Pietro Scaturro, Stephan Urban, Stefan Seitz, Ralf Bartenschlager
{"title":"Hepatitis B virus proteome analysis identifies apolipoprotein C1 facilitating particle production and virus entry","authors":"Shangqing Yang, Firat Nebioglu, Minh Tu Pham, Yen-Chia Lin, Andreas Pichlmair, Shirin Nkongolo, Pietro Scaturro, Stephan Urban, Stefan Seitz, Ralf Bartenschlager","doi":"10.1097/hep.0000000000001864","DOIUrl":"https://doi.org/10.1097/hep.0000000000001864","url":null,"abstract":"Background & Aims: Antiviral therapies targeting hepatitis B virus (HBV) suppress viral replication, but rarely achieve functional cure. Understanding HBV-host cell interaction is crucial for developing novel therapeutic approaches. Here, we report host cell proteins associated with HBV virions and filamentous subviral particles (fSVPs) and characterize one host cell protein, apolipoprotein C1 (ApoC1), mechanistically. Methods: Highly purified HBV virions and fSVPs were obtained by sequential use of several biophysical methods. Particles were analyzed by mass spectrometry and associated proteins were evaluated phenotypically using an HBV infection model. The top hit, ApoC1 was characterized in detail. Results: Alongside the established HBV-associated chaperones HSP90AB1 and HSC70, we identified several apolipoprotein-related factors associated with virions and fSVPs. RNAi-based phenotypic validation identified strongest effects for ApoC1, likely due to two complementary effects. First, ApoC1 depletion reduced intracellular cholesterol level impairing HBV infection and SVP production, which was compensated by exogenous cholesterol addition. Second, ApoC1 that is mainly enriched in high-density lipoprotein (HDL), associates with HBV virions and fSVPs and increases HBV infectivity. The same was found for hepatitis D virus (HDV), a satellite virus utilizing HBV envelopes. Supplementation of exogenous HDL enhanced infection via scavenger receptor class B type 1 (SR-B1), the natural HDL receptor. Consistently, inhibition of SR-B1 suppressed HBV and HDV infection. Conclusions: We established a method for obtaining highly purified HBV virions and fSVPs and identified the HDL component ApoC1 to associate with both particle types. ApoC1 promotes HBV and HDV infection most likely via SR-B1 and facilitates viral entry.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"47 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993736","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 : 2026-09-17DOI: 10.1097/hep.0000000000001869
Elliot B. Tapper, Sumeet Asrani, Ethan Weinberg, Lili Zhao, Samantha Nikirk, Shivang Mehta, Neil B. Alexander, Xi Chen, Donna M. Evon, Marina Serper
{"title":"Lactulose with or without TeleTai-Chi for the prevention of falls: A sequential multiple assignment randomized controlled trial (LiveSMART)","authors":"Elliot B. Tapper, Sumeet Asrani, Ethan Weinberg, Lili Zhao, Samantha Nikirk, Shivang Mehta, Neil B. Alexander, Xi Chen, Donna M. Evon, Marina Serper","doi":"10.1097/hep.0000000000001869","DOIUrl":"https://doi.org/10.1097/hep.0000000000001869","url":null,"abstract":"Background: Falls are common and morbid for patients with cirrhosis, and patients have identified reducing fall risk as an unmet need and care priority. Approach: This is a 24-week two-stage Sequential, Multiple Assignment Randomized Trial (SMART) at four centers in Michigan, Pennsylvania, and Texas enrolling 230 adults with cirrhosis and portal hypertension without prior overt hepatic encephalopathy (HE). There were two stages. In stage 1 (weeks 1–12), participants were randomized to lactulose or enhanced usual care (education on nutrition and fall prevention). In Stage 2 (weeks 13–24), participants were randomized to TeleTai-Chi or enhanced usual care (exercise education). We evaluated the effectiveness of lactulose with-or-without TeleTai-Chi. The primary outcome was a hierarchical composite of death or transplantation, injurious falls, incident HE, and non-injurious falls. We used an intention-to-treat win ratio (WR). Results: Lactulose followed by TeleTai-Chi, compared with enhanced usual care, reduced injurious falls (4% vs. 12%) and non-injurious falls (19% vs. 32%), with no differences in overt HE (2% vs. 0%) or death/transplantation (0% vs. 0%). Compared with non-users, lactulose users experienced fewer injurious falls (3.5% vs. 8.5%), non-injurious falls (15.0% vs. 26.5%), and overt HE (1.8% vs. 2.6%), with no difference in death/transplantation or adverse events resulting in a WR 2.3 95%CI(1.3-4.0). Sequential lactulose/TeleTai-Chi reduced the risk of the primary outcome compared with usual care (WR 2.7 95%CI(1.305.5). Conclusion: In patients with cirrhosis and portal hypertension without prior overt HE, lactulose reduced falls and fall-related harms. Sequential lactulose followed by TeleTai-Chi was also superior to enhanced usual care.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"27 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985116","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 : 2026-09-17DOI: 10.1097/hep.0000000000001867
Xinrui Jin, Terry Cheuk-Fung Yip
{"title":"From meaningful change to reliable response assessment: Editorial on “Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH”","authors":"Xinrui Jin, Terry Cheuk-Fung Yip","doi":"10.1097/hep.0000000000001867","DOIUrl":"https://doi.org/10.1097/hep.0000000000001867","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"59 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985115","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 : 2026-09-15DOI: 10.1097/hep.0000000000001855
Niharika Samala, Melanie G. Cree, Fernando Bril, Ricardo Azziz
{"title":"Polyendocrine metabolic ovarian syndrome (PMOS): The impact of terminology update through the lens of gastroenterology & hepatology","authors":"Niharika Samala, Melanie G. Cree, Fernando Bril, Ricardo Azziz","doi":"10.1097/hep.0000000000001855","DOIUrl":"https://doi.org/10.1097/hep.0000000000001855","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"78 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148973430","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 : 2026-09-15DOI: 10.1097/hep.0000000000001847
Chen Zhang, Nicholas Dunn, Yan Xie, Nicholas O. Davidson, Wei Zhong, Wen-Xing Ding, Hong-Min Ni
{"title":"VPS13D protects against alcohol- associated steatohepatitis by regulating organelle contacts and VLDL secretion","authors":"Chen Zhang, Nicholas Dunn, Yan Xie, Nicholas O. Davidson, Wei Zhong, Wen-Xing Ding, Hong-Min Ni","doi":"10.1097/hep.0000000000001847","DOIUrl":"https://doi.org/10.1097/hep.0000000000001847","url":null,"abstract":"Background: Organelle contact sites are critical for intracellular signaling, membrane dynamics, and organelle quality control. Here we examined the role of VPS13D, a bridge-like lipid transport protein, in alcohol-induced liver injury and defined the mechanisms by which VPS13D regulates lipid metabolism at organelle contact sites. Approach and Results: Liver-specific <jats:italic toggle=\"yes\">Vps13d</jats:italic> knockout ( <jats:italic toggle=\"yes\">LKO</jats:italic> ) mice and matched wild-type (WT) mice were subjected to chronic-plus-binge ethanol feeding. RNA-seq and metabolomic analyses were performed to investigate changes in hepatic gene expression and metabolism. Biochemical, microscopic, and histological analyses were performed to examine organelle contacts and liver injury. Liver samples from patients with alcohol-associated hepatitis (AH) showed decreased VPS13D expression and mitochondrial-ER contact sites. Binge ethanol-fed <jats:italic toggle=\"yes\">Vps13d LKO</jats:italic> mice developed more severe steatosis, inflammation and liver injury, with increased progenitor cells, compared with WT mice. Ethanol-fed <jats:italic toggle=\"yes\">Vps13d LKO</jats:italic> mice exhibited decreased mitochondria-ER contact sites and peroxisome content, with increased lysosome damage and ER stress compared with WT mice. Metabolomic analysis revealed altered hepatic phospholipid homeostasis, with increased hepatic phosphatidylethanolamine (PE) and decreased phosphatidylcholine (PC) abundance, along with decreased phosphatidylethanolamine N-methyltransferase (PEMT) expression, resulting in impaired hepatic VLDL secretion in ethanol-fed <jats:italic toggle=\"yes\">Vps13d LKO</jats:italic> mice. Adenovirus-mediated hepatic PEMT expression increased VLDL secretion and decreased steatosis and liver injury in ethanol-fed <jats:italic toggle=\"yes\">Vps13d LKO</jats:italic> mice. Conclusions: Loss of hepatic VPS13D disrupts mitochondria-ER contact sites, decreasing hepatic PC content and VLDL secretion, promoting ethanol-induced steatosis, progenitor cell accumulation, and liver injury. ER-mitochondrial contact disruption and altered phospholipid homeostasis may be pathogenic drivers in AH.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"59 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148973429","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 : 2026-09-08DOI: 10.1097/hep.0000000000001863
Markus Cornberg, Jordan J. Feld
{"title":"Stopping is only the beginning: Sequential immune therapy after Nucleos(t)ide analogue withdrawal in chronic hepatitis B","authors":"Markus Cornberg, Jordan J. Feld","doi":"10.1097/hep.0000000000001863","DOIUrl":"https://doi.org/10.1097/hep.0000000000001863","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"7 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148909276","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 : 2026-09-08DOI: 10.1097/hep.0000000000001861
Jeffrey V. Lazarus, Christopher J. Kopka, Fasiha Kanwal, Sonal Kumar, Mohamed Hassany
{"title":"AASLD’s opportunity to lead national monitoring of the World Health Assembly resolution on steatotic liver disease","authors":"Jeffrey V. Lazarus, Christopher J. Kopka, Fasiha Kanwal, Sonal Kumar, Mohamed Hassany","doi":"10.1097/hep.0000000000001861","DOIUrl":"https://doi.org/10.1097/hep.0000000000001861","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"3 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148909275","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}