Hepatology最新文献

{"title":"Mechanisms coupling lipid droplets to MASLD pathophysiology.","authors":"Mari V Reid, Gavin Fredickson, Douglas G Mashek","doi":"10.1097/HEP.0000000000001141","DOIUrl":"10.1097/HEP.0000000000001141","url":null,"abstract":"<p><p>Hepatic steatosis, the buildup of neutral lipids in lipid droplets (LDs), is commonly referred to as metabolic dysfunction-associated steatotic liver disease when alcohol or viral infections are not involved. Metabolic dysfunction-associated steatotic liver disease encompasses simple steatosis and the more severe metabolic dysfunction-associated steatohepatitis, characterized by inflammation, hepatocyte injury, and fibrosis. Previously viewed as inert markers of disease, LDs are now understood to play active roles in disease etiology and have significant nonpathological and pathological functions in cell signaling and function. These dynamic properties of LDs are tightly regulated by hundreds of proteins that coat the LD surface, controlling lipid metabolism, trafficking, and signaling. The following review highlights various facets of LD biology with the primary goal of discussing key mechanisms through which LDs promote the development of advanced liver diseases, including metabolic dysfunction-associated steatohepatitis.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"273-291"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542354","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":"What's in a name? Reframing pediatric fatty liver disease in the Era of MASLD.","authors":"Mian B Khalid, Sumera I Ilyas","doi":"10.1097/HEP.0000000000001783","DOIUrl":"10.1097/HEP.0000000000001783","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"84 1","pages":"3-4"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256582","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":"HBV induces liver fibrosis through the generation of reactive oxygen species in a pyruvate-dependent manner.","authors":"Xiaoqiong Duan, Shasha Li, Qingyuan Li, Wenxian Wen, Olivia Mezzetti, Charlotte Warner, Min Xu, Andre J Jeyarajan, Yujia Li, Yaoqiang Shi, Ning Jiang, Wenting Li, Chunhui Yang, Youmin Yang, Jing Xu, Min Xu, He Xie, Shilin Li, Raymond T Chung, Xianding Wang, Limin Chen, Wenyu Lin","doi":"10.1097/HEP.0000000000001597","DOIUrl":"10.1097/HEP.0000000000001597","url":null,"abstract":"<p><strong>Background and aims: </strong>Chronic hepatitis B (CHB) is a major etiology of liver cirrhosis. We previously found that pyruvate, a key intermediate in many metabolic pathways, increases HBV replication. However, the mechanism by which pyruvate mediates HBV-induced liver fibrosis is not well characterized. We hypothesize that HBV induces liver fibrosis through a pyruvate-peroxisome proliferator-activated receptor α (PPARα)-reactive oxygen species (ROS) pathway.</p><p><strong>Approach and results: </strong>We evaluated HBV-induced fibrogenesis in HepAD38, HBV-infected NTCP-HepG2, primary human hepatocytes (PHHs), and HSC lines (LX2) in mono-culture and co-culture models and in patient sera. We also evaluated the effects of PPARα agonist/antagonist and ROS inhibition on HBV-induced liver fibrosis in cell culture, HBV carrier mouse, HBV-Transgenic mouse (HBV-Tg), humanized liver mouse, and human precision-cut liver slice (PCLS) models. We found that HBV increased pyruvate levels and fibrosis-related gene expression in both HBV-infected hepatocytes and patient sera. Supernatants from HBV-infected cells (HBVsup) and pyruvate supplementation independently and additively increased expression of profibrotic genes (TGF-β1, TIMP-1, COL1A1, and α-SMA), activated ROS production, and inhibited PPARα expression. Notably, PPARα inhibition and siRNA knockdown increased ROS production and profibrogenic gene expression, while activation of PPARα blocked HBVsup-induced and pyruvate-induced ROS generation and fibrogenesis. ROS was confirmed to be downstream of PPARα-related fibrogenesis, as ROS inhibition abrogated HBVsup-induced, pyruvate supplementation-induced, or PPARα inhibition-induced liver fibrosis.</p><p><strong>Conclusions: </strong>HBV infection induces pyruvate production and decreases PPARα expression, leading to increased ROS generation and liver fibrosis. Pyruvate and PPARα represent novel targets for antifibrotic therapeutic development in CHB.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"216-232"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601543","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: Clarifying endothelial specificity and hemodynamic coupling of the miR-153-3p-pyroptosis axis.","authors":"Dandan Weng","doi":"10.1097/HEP.0000000000001629","DOIUrl":"10.1097/HEP.0000000000001629","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E18-E19"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761724","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":"Predictors of fibrosis, clinical events, and mortality in MASLD: Data from the Global-MASLD study.","authors":"Zobair M Younossi, Leyla de Avila, Salvatore Petta, Hannes Hagström, Seung Up Kim, Atsushi Nakajima, Javier Crespo, Laurent Castera, Naim Alkhouri, Ming-Hua Zheng, Sombat Treeprasertsuk, Prooksa Ananchuensook, Shalimar, Emmanuel Tsochatzis, Shenoy Kotacherry Trivikrama, Leena Kondarappassery Balakumaran, Jian-Gao Fan, Stuart K Roberts, Khalid Alswat, Vincent Wai-Sun Wong, Yusuf Yilmaz, Winston Dunn, Sven Francque, Ahmed Cordie, Ming-Lung Yu, Mattias Ekstedt, George Boon-Bee Goh, Claudia P Oliveira, Mario Guimaraes Pessoa, Wah Kheong Chan, Marlen Ivon Castellanos Fernandez, Ajay Duseja, Juan Pablo Arab, George Papatheodoridis, Giada Sebastiani, Cristiane Villela-Nogueira, Roberta D'Ambrosio, Pietro Lampertico, Khalid M AlNaamani, A G Holleboom, Arun Valsan, Arathi Venu, Mohamed El-Kassas, Grazia Pennisi, Ying Shang, Wen-Yue Liu, Hye Won Lee, Takashi Kobayashi, Satoru Kakizaki, Cyrielle Caussy, Brian Pearlman, Paula Iruzubieta, Rida Nadeem, Felice Cinque, Antonia Neonaki, Mirko Zoncapé, Rui-Xu Yang, Sherlot Juan Song, Nicholas Dunn, Zouhir Gadi, Ming-Lun Yeh, Kevin Kim-Jun Teh, Sanjiv Mahadeva, Licet Gonzalez Fabian, Ahmed Almohsen, Nathalie Leite, Nicola Pugliese, Johan Vessby, Chencheng Xie, Narendra Singh Choudhary, Ethan Friend, Maria Poca, Takumi Kawaguchi, Francesco Paolo Russo, Adrian Gadano, Luis Antonio Diaz, Ashwani K Singal, Berenice Segrestin, Nadege Gunn, Didac Mauricio, Marco Arrese, Anna Fracanzani, Rosa Lombardi, Brian Lam, Andrei Racila, Saleh A Alqahtani, Maria Stepanova","doi":"10.1097/HEP.0000000000001617","DOIUrl":"10.1097/HEP.0000000000001617","url":null,"abstract":"<p><strong>Background and aims: </strong>Advanced histologic fibrosis is a major predictor of mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to identify advanced fibrosis clinical determinants across diverse MASLD populations and to assess the prognostic value of noninvasive markers (NITs) of fibrosis for adverse outcomes.</p><p><strong>Approach and results: </strong>The Global MASLD (G-MASLD) enrolled biopsy-confirmed MASLD patients with clinical, histologic, and noninvasive test (NIT) data. Factors associated with the presence of advanced histologic fibrosis (F3-F4) in MASLD and clinical outcomes were assessed. There were 17,792 patients with MASLD. Advanced fibrosis (≥F3) was present in 35%. The prevalence of type 2 diabetes (T2D) increased stepwise with fibrosis stage, from 28% in F0 to 70% in F4 (trend p <0.0001). Independent predictors of advanced fibrosis included older age, T2D, and obesity, although the association with obesity varied by region. Among patients with follow-up (mean 6.6 y), 6.5% died and 10.1% experienced a clinical event. Older age, male sex, T2D, and obesity were independent predictors of both mortality and clinical events ( p <0.05). Fibrosis severity, whether defined histologically or by NITs, was strongly associated with higher risks of death and liver-related outcomes (all adjusted HR>1.0, p <0.001). Five-year mortality was 2.1% overall, rising to 8.3% in patients with cirrhosis, and exceeded 10% among those with high-risk NIT score values.</p><p><strong>Conclusions: </strong>In this large global biopsy-based MASLD cohort, advanced fibrosis was highly prevalent and strongly linked to T2D. Both histologic fibrosis and NITs were independent predictors of mortality and clinical outcomes, underscoring the prognostic value of fibrosis assessment with NITs.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"204-215"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511190","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: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease.","authors":"Jing Liu, Guo-Ming Zhang","doi":"10.1097/HEP.0000000000001663","DOIUrl":"10.1097/HEP.0000000000001663","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E14-E15"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861371","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":"Good vibrations: Using VCTE to predict hepatic decompensation in MASLD.","authors":"Krishan S Patel, Juan Pablo Arab","doi":"10.1097/HEP.0000000000001709","DOIUrl":"10.1097/HEP.0000000000001709","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"84 1","pages":"7-8"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256644","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: Comments on the Study-Body size disparities limit women's access to liver transplantation under the MELD 3.0 scoring system.","authors":"Jiahang He, Qing Xie, Zhujun Cao","doi":"10.1097/HEP.0000000000001616","DOIUrl":"10.1097/HEP.0000000000001616","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E13"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487285","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: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease.","authors":"Peng Zhang, Grace L Su","doi":"10.1097/HEP.0000000000001664","DOIUrl":"10.1097/HEP.0000000000001664","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E16-E17"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861339","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":"Endothelial-to-mesenchymal transition: A targetable mechanism that contributes to portal vein thrombosis in cirrhosis.","authors":"Aina Anton, Sarah Shalaby, María Luisa Botero, Annabel Blasi, Yiliam Fundora, Sergio Barace, Rosa Montañés, Héctor García-Calderó, Maria Velasco-de Andrés, Lara Orts, Hasanka Madubashetha, Carla Montironi, Pol Olivas, Gonzalo Crespo, Cynthia Bazán, Rommel Zambrano-Huailla, Peio Aristu Zabalza, Josepmaria Argemí, Scott L Friedman, Juan Carles García-Pagán, Genís Campreciós, Virginia Hernández-Gea","doi":"10.1097/HEP.0000000000001547","DOIUrl":"10.1097/HEP.0000000000001547","url":null,"abstract":"<p><strong>Background and aims: </strong>Portal vein thrombosis (PVT) is a frequent complication of cirrhosis, yet its pathophysiology remains elusive. Unlike thrombosis in other vascular beds, anticoagulation often fails to completely recanalize PVT, highlighting the need for greater mechanistic insight and alternative therapeutic approaches. Our study aimed to characterize the structural and cellular changes in the portal venous vascular bed to identify novel physiologically driven therapeutic targets.</p><p><strong>Approach and results: </strong>Portal vein tissue specimens from explanted livers of patients with cirrhosis with and without PVT and from liver donors were histologically analyzed. PVT is associated with a remarkable eccentric thickening of the tunica intima due to accumulation of extracellular material and tunica intima increased cellularity. Transcriptomic analysis of human portal vein endothelial cells (PVEC) from patients with PVT identified the endothelial-to-mesenchymal transition (EndMT) pathway upregulated in PVECs from patients with PVT. In silico drug repurposing analysis identified statins as potential agents targeting these alterations. In vitro treatment with statins attenuated hallmarks of EndMT in primary human PVECs.</p><p><strong>Conclusions: </strong>In cirrhosis, the portal vein endothelium undergoes maladaptive remodeling marked by eccentric intimal hyperplasia, driven by ECM accumulation and infiltration of inflammatory and myofibroblast-like cells. This process narrows the lumen and may promote PVT. EndMT plays a key role in this transformation and emerges as a novel and promising therapeutic target. Notably, statins can attenuate EndMT, highlighting its potential in PVT treatment.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"91-105"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375851","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}