JHEP Reports最新文献

{"title":"Spatial immune scoring and prediction of HCC outcomes","authors":"Marta Piqué-Gili , Daniela Sia","doi":"10.1016/j.jhepr.2025.101476","DOIUrl":"10.1016/j.jhepr.2025.101476","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101476"},"PeriodicalIF":9.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656424","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":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00181-8","DOIUrl":"10.1016/S2589-5559(25)00181-8","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101503"},"PeriodicalIF":9.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572391","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(25)00178-8","DOIUrl":"10.1016/S2589-5559(25)00178-8","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101500"},"PeriodicalIF":9.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572389","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":"Myeloid TGF-β signaling shapes liver macrophage heterogeneity and metabolic liver disease pathogenesis","authors":"Ziyi Meng ,&nbsp;Xiaoxue Qiu ,&nbsp;Zhimin Chen ,&nbsp;Yu-tung Lee ,&nbsp;Linkang Zhou ,&nbsp;You Lu ,&nbsp;Tongyu Liu ,&nbsp;Siming Li ,&nbsp;Benjamin Levi ,&nbsp;Katherine A. Gallagher ,&nbsp;Jiandie D. Lin","doi":"10.1016/j.jhepr.2025.101488","DOIUrl":"10.1016/j.jhepr.2025.101488","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Cellular heterogeneity of innate immune cells, such as macrophages, in the liver is a hallmark of metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis. However, the mechanisms shaping liver macrophage heterogeneity and function during disease progression remain poorly understood.</div></div><div><h3>Methods</h3><div>Control or myeloid-specific <em>Tgfbr1</em> knockout mice (n = 9-12 per group) were fed a 12-week choline-deficient, amino acid-defined high-fat diet (CDA-HFD) or a 20-week GAN diet (40% fat, 22% fructose, 2% cholesterol). Liver tissue was analyzed using histopathology, quantitative PCR, immunoblotting, flow cytometry, and RNA sequencing (RNA-seq). Bulk RNA-seq (n = 3 per group) and single-nucleus RNA-seq were performed to investigate transcriptional reprogramming. Macrophage population dynamics were evaluated by flow cytometry and immunofluorescence.</div></div><div><h3>Results</h3><div>We identified TGF-β signaling as a crucial regulator of disease-associated expansion of Trem2⁺ and Fcrl5⁺ macrophages in MASH livers. Myeloid-specific inactivation of <em>Tgfbr1</em> in mice exacerbated diet-induced MASH, with increased hepatocyte injury, inflammation, and liver fibrosis. Mechanistically, loss of TGF-β signaling in myeloid cells altered macrophage composition, marked by a reduction in Trem2⁺ and expansion of Fcrl5⁺ macrophages. Additionally, macrophages lacking <em>Tgfbr1</em> exhibited gene signatures associated with inflammasome activation, cytokine signaling, cellular senescence, and immunosuppression. These changes in macrophage composition and function promoted effector T cell exhaustion and the development of MASH-associated hepatocellular carcinoma in <em>Tgfbr1</em>-deficient mice.</div></div><div><h3>Conclusions</h3><div>These findings identify myeloid TGF-β signaling as a key driver of liver macrophage heterogeneity and polarization within the microenvironment during the progression of MASH and MASH-associated liver cancer.</div></div><div><h3>Impact and implications</h3><div>Our study reveals that myeloid TGF-β signaling plays a crucial role in shaping liver macrophage heterogeneity, which in turn influences the pathogenesis of metabolic liver disease. These findings are particularly important for researchers studying immune-metabolic interactions and for clinicians seeking new therapeutic strategies for liver disorders. By elucidating how TGF-β signaling regulates macrophage function, our work paves the way for targeted interventions that modulate immune responses to improve liver health. Future research should consider the potential translational applications of these findings while addressing limitations related to model systems and human variability.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101488"},"PeriodicalIF":9.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633293","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":"Consistent improvements in liver histology across subgroups in a post hoc analysis of the SYNERGY-NASH trial with tirzepatide","authors":"Mark L. Hartman ,&nbsp;Rohit Loomba ,&nbsp;Eric J. Lawitz ,&nbsp;Raj Vuppalanchi ,&nbsp;Jérôme Boursier ,&nbsp;Elisabetta Bugianesi ,&nbsp;Masato Yoneda ,&nbsp;Yuanyuan Tang ,&nbsp;Bram Brouwers ,&nbsp;Mathijs C. Bunck ,&nbsp;Axel Haupt ,&nbsp;Arun J. Sanyal","doi":"10.1016/j.jhepr.2025.101472","DOIUrl":"10.1016/j.jhepr.2025.101472","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>In the SYNERGY-NASH trial for metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis, tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, effectively resolved MASH without worsening fibrosis in up to 73% of patients. We explored the extent of histological improvements across clinically relevant subgroups in this trial.</div></div><div><h3>Methods</h3><div>Participants (n = 190) were randomly assigned 1:1:1:1 to receive once-weekly subcutaneous tirzepatide (5, 10, or 15 mg) or placebo for 52 weeks. We analyzed 155 participants who completed the study on treatment with evaluable end-of-treatment biopsies. <em>Post hoc</em> subgroups (n = 34) were defined by demographics, histology, serum, and imaging biomarkers using the median of baseline values for continuous variables. Risk differences (RDs) <em>vs.</em> placebo (95% CI) were calculated using a logistic regression model.</div></div><div><h3>Results</h3><div>Compared with placebo, tirzepatide was consistently associated with improved MASH resolution without worsening fibrosis across subgroups defined by sex, age, ethnicity, BMI, type 2 diabetes status, histological disease activity, fibrosis stage, serum aminotransferases, serum biomarkers of fibrosis and MASH, and imaging assessments of liver fat, fibroinflammation, and stiffness. For tirzepatide 5, 10 and 15 mg, RDs were statistically significant (<em>p &lt;</em>0.05) for 74%, 97%, and 100% of the subgroups, respectively. While most RDs for fibrosis improvement without worsening of MASH favored tirzepatide, statistical significance was not reached in 59–79% of subgroups due to limited sample sizes. Significant fibrosis improvement (<em>p &lt;</em>0.05) was observed with tirzepatide 5 and 15 mg among participants with stage 3 fibrosis.</div></div><div><h3>Conclusion</h3><div>These <em>post hoc</em> analyses suggest that tirzepatide was consistently associated with improved MASH resolution without worsening of fibrosis across subgroups defined by demographics, histology, and biomarkers, compared with placebo.</div></div><div><h3>Impact and implications</h3><div>In participants with metabolic dysfunction-associated steatohepatitis (MASH), tirzepatide demonstrated superiority to placebo for resolution of MASH without worsening of fibrosis, but the extent of MASH resolution across clinically relevant subgroups was not reported. In these <em>post hoc</em> analyses, we show that tirzepatide was consistently associated with improved MASH resolution without worsening of fibrosis across subgroups defined by demographics, histology, serum biomarkers, and imaging tests. These data support further investigation of tirzepatide in larger studies of participants with MASH including representation from diverse populations.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101472"},"PeriodicalIF":9.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597383","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":"Corrigendum to ‘B-cell activating factor and IL-21 levels predict treatment response in autoimmune hepatitis’ [J Hepatol (2022) doi: 10.1016/j.jhepr.2022.100460]","authors":"Maaike Biewenga ,&nbsp;Sebastiaan Heidt ,&nbsp;Manon Vergunst ,&nbsp;Camiel J.M. Marijnissen ,&nbsp;Rob A. de Man ,&nbsp;Annemiek A. van der Eijk ,&nbsp;Adriaan J. van der Meer ,&nbsp;Leendert A. Trouw ,&nbsp;Bart van Hoek","doi":"10.1016/j.jhepr.2025.101447","DOIUrl":"10.1016/j.jhepr.2025.101447","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101447"},"PeriodicalIF":9.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205535","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":"Comment on opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis","authors":"Emmanuel Gonzales ,&nbsp;Richard J. Thompson ,&nbsp;Emmanuel Jacquemin","doi":"10.1016/j.jhepr.2025.101361","DOIUrl":"10.1016/j.jhepr.2025.101361","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101361"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221599","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":"Erratum to ‘Use of artificial intelligence for liver diseases: A survey from the EASL congress 2024’ [JHEP Reports (2024) doi https://doi.org/10.1016/j.jhepr.2024.101209]","authors":"Laura Žigutytė ,&nbsp;Thomas Sorz-Nechay ,&nbsp;Jan Clusmann ,&nbsp;Jakob Nikolas Kather","doi":"10.1016/j.jhepr.2025.101446","DOIUrl":"10.1016/j.jhepr.2025.101446","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101446"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221600","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":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00139-9","DOIUrl":"10.1016/S2589-5559(25)00139-9","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101461"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221601","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(25)00137-5","DOIUrl":"10.1016/S2589-5559(25)00137-5","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101459"},"PeriodicalIF":9.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221550","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}