Hepatology最新文献

{"title":"Platelets harness innate immunity to promote the dissemination of HCC.","authors":"Stefania Mantovani, Mario U Mondelli","doi":"10.1097/HEP.0000000000000946","DOIUrl":"10.1097/HEP.0000000000000946","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"757-759"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174058","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":"Management of patients with advanced HCC receiving atezolizumab/bevacizumab: Take care of cirrhosis!","authors":"Jean-Charles Nault, Massimo Iavarone","doi":"10.1097/HEP.0000000000001047","DOIUrl":"10.1097/HEP.0000000000001047","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"760-761"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896173","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":"Noninvasive liver disease assessment to identify portal hypertension: Systematic and narrative reviews supporting the AASLD Practice Guideline.","authors":"Don C Rockey, Mouaz Alsawas, Andres Duarte-Rojo, Keyur Patel, Deborah Levine, Sumeet K Asrani, Bashar Hasan, Tarek Nayfeh, Yahya Alsawaf, Samer Saadi, Konstantinos Malandris, M Hassan Murad, Richard K Sterling","doi":"10.1097/HEP.0000000000000841","DOIUrl":"10.1097/HEP.0000000000000841","url":null,"abstract":"<p><strong>Background and aims: </strong>Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed.</p><p><strong>Approach and results: </strong>We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50%, while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa.</p><p><strong>Conclusions: </strong>While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1086-1104"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136302","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":"Conserved long noncoding RNA TILAM promotes liver fibrosis through interaction with PML in HSCs.","authors":"Cheng Sun, Chan Zhou, Kaveh Daneshvar, Amel Ben Saad, Arcadia J Kratkiewicz, Benjamin J Toles, Nahid Arghiani, Anja Hess, Jennifer Y Chen, Joshua V Pondick, Samuel R York, Wenyang Li, Sean P Moran, Stefan D Gentile, Raza Ur Rahman, Zixiu Li, Peng Zhou, Robert P Sparks, Tim Habboub, Byeong-Moo Kim, Michael Y Choi, Silvia Affo, Robert F Schwabe, Yury V Popov, Alan C Mullen","doi":"10.1097/HEP.0000000000000822","DOIUrl":"10.1097/HEP.0000000000000822","url":null,"abstract":"<p><strong>Background and aims: </strong>Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies.</p><p><strong>Approach and results: </strong>We identified long noncoding RNA TILAM located near COL1A1 , expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog ( Tilam ), generated Tilam- deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam -deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-β2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs.</p><p><strong>Conclusions: </strong>TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"853-869"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334128","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":"Reduction of Z alpha-1 antitrypsin polymers in human iPSC-hepatocytes and mice by LRRK2 inhibitors.","authors":"Deniz Kent, Soon Seng Ng, Adam M Syanda, Payam Khoshkenar, Riccardo Ronzoni, Chao Zheng Li, Marina Zieger, Cindy Greer, Stephanie Hatch, Joe Segal, Samuel J I Blackford, Yu Ri Im, Vivek Chowdary, Taylor Ismaili, Davide Danovi, Patrick A Lewis, James A Irving, Sunil Sahdeo, David A Lomas, Daniel Ebner, Christian Mueller, S Tamir Rashid","doi":"10.1097/HEP.0000000000000969","DOIUrl":"10.1097/HEP.0000000000000969","url":null,"abstract":"<p><strong>Background: </strong>Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by the inheritance of the serpin family A member 1 \"Z\" genetic variant driving alpha-1 antitrypsin (AAT) protein misfolding in hepatocytes. There are no approved medicines for this disease.</p><p><strong>Methods: </strong>We conducted a high-throughput image-based small molecule screen using patient-derived induced pluripotent stem cell-hepatocytes (iPSC-hepatocytes). Identified targets were validated in vitro using 3 independent patient iPSC lines. The effects of the identified target, leucine-rich repeat kinase 2 (LRRK2), were further evaluated in an animal model of A1ATD through histology and immunohistochemistry and in an autophagy-reporter line. Autophagy induction was assessed through immunoblot and immunofluorescence analyses.</p><p><strong>Results: </strong>Small-molecule screen performed in iPSC-hepatocytes identified LRRK2 as a potentially new therapeutic target. Of the commercially available LRRK2 inhibitors tested, we identified CZC-25146, a candidate with favorable pharmacokinetic properties, as capable of reducing polymer load, increasing normal AAT secretion, and reducing inflammatory cytokines in both cells and PiZ mice. Mechanistically, this effect was achieved through the induction of autophagy.</p><p><strong>Conclusions: </strong>Our findings support the use of CZC-25146 and leucine-rich repeat kinase-2 inhibitors in hepatic proteinopathy research and their further investigation as novel therapeutic candidates for A1ATD.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"903-916"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490143","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":"Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.","authors":"Do-Youn Oh, Masafumi Ikeda, Choong-Kun Lee, Carlos Rojas, Chih-Hung Hsu, Jin Won Kim, Lin Shen, Junji Furuse, Joon Oh Park, Mitesh Borad, Filippo de Braud, John Bridgewater, Sunyoung S Lee, Markus Moehler, Francois Audhuy, Motonobu Osada, Masashi Sato, Changhoon Yoo","doi":"10.1097/HEP.0000000000000965","DOIUrl":"10.1097/HEP.0000000000000965","url":null,"abstract":"<p><strong>Background and aims: </strong>We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer.</p><p><strong>Approach and results: </strong>This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer. Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m 2 +cisplatin 25 mg/m 2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149). The primary end point was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survival events had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable]) and placebo (11.5 mo [10.0-not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66-2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively.</p><p><strong>Conclusions: </strong>BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"823-836"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320086","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: Optimizing MASLD treatment - A \"lead-in phase\" before resmetirom.","authors":"Paula Iruzubieta, Marta Alonso, Carolina Jimenez, Javier Crespo","doi":"10.1097/HEP.0000000000001263","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001263","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456418","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":"Health-related quality of life is impaired in people with autoimmune hepatitis: Results of a multicentre cross-sectional study within the European Reference Network","authors":"Romée J.A.L.M. Snijders, Maciej K. Janik, Meike Mund, Natalie Uhlenbusch, Joanna Raszeja-Wyszomirska, Alessio Gerussi, Francesca Bolis, Laura Cristoferi, Pietro Invernizzi, Patricia Kovats, Mária Papp, Lisbet Grønbæk, Henning Grønbæk, Eric T.T.L. Tjwa, Luise Aamann, Henriette Ytting, Vincenzo Ronca, Kathryn Olsen, Ye H. Oo, Adriaan J. van der Meer, João Madaleno, Bernardo Canhão, Bastian Engel, Alejandro Campos-Murguia, Richard Taubert, Özgür M. Koc, Matthijs Kramer, José A. Willemse, Bernd Löwe, Ansgar W. Lohse, Joost P.H. Drenth, Christoph Schramm, Piotr Milkiewicz, Tom J. Gevers","doi":"10.1097/hep.0000000000001271","DOIUrl":"https://doi.org/10.1097/hep.0000000000001271","url":null,"abstract":"Background: Impaired health-related quality of life (HRQoL) contributes to the overall disease burden in autoimmune hepatitis (AIH). This study aimed to evaluate HRQoL in people with AIH and to identify potentially modifiable factors associated with impaired HRQoL using validated patient-reported outcome measures. Methods: Adult AIH patients diagnosed at 12 European centers were enrolled in this prospective, cross-sectional study from July 2020-June 2023. HRQoL was assessed using the Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-item Short Form Health Survey (SF-12), and the European Quality-of-life 5-Dimension 5-Level (EQ-5D-5L) utility index (UI) score. Mixed-model regression analyses identified factors associated with HRQoL and somatic symptom severity. Controls were recruited from the general population in five European countries. Results: A total of 882 patients with AIH (mean age: 51.0 y [SD 17.0]; 76.4% female) and 178 controls were included. Physical but not mental HRQoL was impaired in the AIH group compared with the control group (PCS: 46.3 vs. 51.9, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001; EQ-5D UI: 0.87 vs. 0.95, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). HRQoL was associated with severe somatic symptoms (PCS β=−4.26, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001), fatigue (PCS β=−0.25, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001; MCS β=−0.25, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001), and depression/anxiety (PCS β=−3.37, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001; MCS β=−6.79, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). A complete biochemical response was associated with a lower somatic symptom severity (odds ratio 0.69, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.05). Conclusions: People with AIH had impaired HRQoL compared with controls, particularly in terms of physical well-being. HRQoL scores are associated with symptom burden, encompassing both somatic and psychosocial dimensions.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451645","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":"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":"https://doi.org/10.1097/HEP.0000000000001273","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-02-18","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}

{"title":"Reply: Liver transplantation for primary and secondary liver tumors - patient level meta-analyses compared to UNOS conventional indications.","authors":"Ruben Ciria, Daniel Aliseda, Giammauro Berardi, Fernando Rotellar, Gonzalo Sapisochin","doi":"10.1097/HEP.0000000000001272","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001272","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439709","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}