JHEP Reports最新文献

{"title":"LSECtin attenuates hepatic Th17 expansion in a murine model of cirrhosis and signals through the LAG-3 receptor","authors":"Sebastián Martínez-López , Oriol Juanola , Isabel Gómez-Hurtado , Enrique Ángel-Gomis , Paula Boix , Anabel Fernández-Iglesias , Alex Gallardo-Cruz , Francisco Javier Cubero , Jordi Gracia-Sancho , Amaya Puig-Kröger , Esther Caparrós , Rubén Francés","doi":"10.1016/j.jhepr.2025.101482","DOIUrl":"10.1016/j.jhepr.2025.101482","url":null,"abstract":"<div><h3>Background & Aims</h3><div>LSECtin downregulation during cirrhosis progression is associated with adaptive T-cell expansion. We analyzed the molecular mechanism for LSECtin modulation of Th17 proliferation in an experimental cirrhosis model.</div></div><div><h3>Methods</h3><div>A transgenic mouse model of Clec4g/LSECtin overexpression (Clec4g KI) was subjected to CCl<sub>4</sub>-induced cirrhosis. Cell death, liver function, and inflammation markers (n = 6/group) were evaluated. LSECtin-LAG3 signaling in Th17-differentiated spleen cells (n = 5) and LAG3 expression in livers of human individuals with cirrhosis (n = 6) were also characterized.</div></div><div><h3>Results</h3><div>Densitometred LSECtin expression was significantly downregulated during cirrhosis in wild-type but not Clec4g-KI mice (0.6 ± 0.2 <em>vs.</em> 2.3 ± 0.6 AU, <em>p</em> = 0.001). LSECtin overexpression in cirrhotic mice resulted in less histological damage and improved liver enzyme levels (alanine aminotransferase: 152.7 ± 66.3 <em>vs.</em> 76.33 ± 13.33 U/L, <em>p</em> = 0.004). Cell-death pathway analysis revealed no differences in apoptosis markers <em>Casp3</em> and <em>Casp8</em> but reduced levels of necroptotic intermediates <em>Mlkl</em> and <em>Ripk3</em>. LSECtin overexpression reduced hepatic leukocyte infiltration and enriched the differentiation from inflammatory Rorgt<sup>+</sup>/IL-17<sup>+</sup> (2.4 ± 0.8 <em>vs.</em> 7.7 ± 3.5% CD4<sup>+</sup>, <em>p</em> = 0.043) to regulatory Foxp3<sup>+</sup>/IL-10<sup>+</sup> cells (3.6 ± 0.9 <em>vs.</em> 1.2 ± 0.7% CD4<sup>+</sup>, <em>p</em> = 0.047) in cirrhotic animals. LSECtin interacted with LAG-3 on polarized spleen-derived CD4<sup>+</sup> T cells, inhibiting Th17 differentiation (10.5 ± 2.7 <em>vs.</em> 6.6 ± 2.1% CD4<sup>+</sup>, <em>p</em> = 0.037) by suppressing Stat3 and Zap70 pathways. LSECtin did not restrain the Th17 subset expansion during LAG3 blockade (6.6 ± 2.1 <em>vs.</em> 14.2 ± 4.0% CD4<sup>+</sup>, <em>p</em> = 0.005). Livers of human individuals with cirrhosis showed increased LAG-3-expressing Th17 cells compared with controls (3.2 ± 1.4 <em>vs.</em> 0.1 ± 0.1 cells/mm<sup>2</sup>, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>We have established a valuable murine model of LSECtin overexpression to assess its impact on hepatic inflammation during cirrhosis. LAG-3 was identified as the molecular mechanism by which LSECtin attenuates Th17 differentiation. Given LSECtin capacity to modulate the Th profile and decrease proinflammatory cell death, liver-directed molecular approaches to restore its expression may be of therapeutic interest during cirrhosis.</div></div><div><h3>Impact and implications</h3><div>LSECtin downregulation is associated with the expansion of Th17 cell subpopulation during cirrhosis. Findings highlight the crucial role of LSECtin in regulating immune responses and mitigating liver damage in cirrhosis. Restoring LSECtin expression through targeted li","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"Article 101482"},"PeriodicalIF":7.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749590","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":"All-cause and disease-specific mortality in young adults with MASLD: A nationwide cohort study.","authors":"Jeayeon Park, Goh Eun Chung, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho","doi":"10.1016/j.jhepr.2025.101477","DOIUrl":"10.1016/j.jhepr.2025.101477","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major cause of chronic liver disease globally, particularly among young adults. We aimed to analyze all-cause and disease-specific mortality in young adults with MASLD.</p><p><strong>Methods: </strong>In this nationwide cohort study, we analyzed data from the Korean National Health Insurance Service, focusing on individuals aged 20 to 39 years who underwent health screenings between 2009 and 2012. The participants were categorized into two groups: those with MASLD and those without steatotic liver disease (SLD). SLD was defined by a fatty liver index ≥30. Mortality risk was analyzed via Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 5,699,047 participants were included in the study, 25.4% of whom had MASLD. During a median follow-up of 10.6 years (interquartile range, 9.5-11.2), all-cause death occurred in 11,706 (0.8%) participants in the MASLD group and in 19,611 (0.5%) in the non-SLD group. Young adults with MASLD had a significantly greater risk of all-cause mortality than those without steatosis (adjusted hazard ratio [aHR], 1.15; 95% CI 1.12-1.19). The MASLD group also had an increased risk of mortality related to cardiovascular disease, liver cancer, and liver disease, whereas the risk of extrahepatic cancer-related mortality did not significantly differ between the two groups. Compared to men with MASLD, women with MASLD had higher risks of all-cause, cardiovascular, extrahepatic cancer, and liver disease-related mortality, although the risk of liver cancer-related mortality was similar between the sexes.</p><p><strong>Conclusion: </strong>Young adults with MASLD are at a significantly increased risk of all-cause and disease-specific mortality. These findings underscore the importance of early detection and intervention to mitigate the long-term outcomes of MASLD in young adults.</p><p><strong>Impact and implications: </strong>Global increases in obesity among adolescents and young adults are driving an increase in the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in these populations. In this nationwide cohort study, young adults with MASLD were found to have a significantly greater risk of all-cause mortality, as well as mortality related to cardiovascular disease, liver cancer, and liver disease than those without steatosis. Therefore, early detection and timely intervention for MASLD in young adults are crucial to improving clinical outcomes and reducing the global burden of the disease.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"101477"},"PeriodicalIF":7.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873258","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":"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":"Missed opportunities in HCV care: Trends in late diagnosis and treatment.","authors":"Shane Tillakeratne, Heather Valerio, Maryam Alavi, Behzad Hajarizadeh, Marianne Martinello, Kathy Petoumenos, Jacob George, Janaki Amin, Gail V Matthews, Jason Grebely, Sallie-Anne Pearson, Gregory J Dore","doi":"10.1016/j.jhepr.2025.101474","DOIUrl":"10.1016/j.jhepr.2025.101474","url":null,"abstract":"<p><strong>Background & aims: </strong>Timely HCV care is essential to prevent liver disease progression. The aim of this study was to evaluate trends in late HCV diagnosis and treatment in people diagnosed with end-stage liver disease (ESLD) in New South Wales (NSW), Australia.</p><p><strong>Methods: </strong>HCV notifications in NSW, Australia (1995-2022) were linked to hospital admissions (2010-2021) and treatment records (2002-2022). Descriptive analyses and logistic regression were used to examine trends and factors associated with late diagnosis and missed treatment opportunities. Late diagnosis and treatment were defined as the absence of HCV notification and treatment within 2 years prior to or following the first hospitalisation for ESLD.</p><p><strong>Results: </strong>Among 4,419 people with an HCV notification and ESLD diagnosis, late HCV diagnoses decreased from 24% in 2010-2012 to 16% in 2019-2021. The proportion receiving no or late treatment declined from 98% (85% no, 13% late) to 70% (48% no, 22% late). Residing in rural or regional areas was linked with late HCV diagnosis (adjusted odds ratio [aOR] 1.44, 95% CI 1.05-1.97, <i>p</i> = 0.024). Recent injecting drug use (aOR 0.78, 95% CI 0.60-0.99, <i>p</i> = 0.041), incarceration (distant [aOR 0.55, 95% CI 0.38-0.78, <i>p</i> = 0.001], recent [aOR 0.51, 95% CI 0.28-0.96, <i>p</i> = 0.037]), government assistance (aOR 0.57, 95% CI 0.39-0.82, <i>p</i> = 0.002), and older age (born ≤1944 [aOR 0.31, 95% CI 0.15-0.66, <i>p</i> = 0.002], born 1945-1959 [aOR 0.47, 95 CI% 0.29-0.77, <i>p</i> = 0.003]), were associated with lower odds of a late HCV diagnosis. Recent alcohol use disorder was associated with increased odds of no or late treatment (aOR 1.80, 95% CI 1.40-2.32, <i>p</i> = 0.001).</p><p><strong>Conclusion: </strong>Encouragingly, factors associated with social marginalisation predict earlier HCV diagnosis, while rural/regional residence predicts late HCV diagnosis among people with ESLD. Missed HCV treatment opportunity, defined by no or late treatment is associated with alcohol use disorder, but not with indicators of social marginalisation.</p><p><strong>Impact and implications: </strong>Timely HCV care is essential to prevent liver disease progression. Significant improvements in HCV diagnosis and treatment timing in New South Wales over the past decade highlight the success of Australia's universal provision of direct-acting antiviral therapy and targeted screening initiatives, particularly for people who inject drugs and those recently incarcerated. Persistent barriers to timely care remain for rural communities and people with alcohol use disorder, suggesting the need for enhanced integration of HCV services with alcohol treatment programs and expanded rural outreach. Achieving World Health Organization elimination targets by 2030 requires strengthened efforts to reach underserved populations and better integrate HCV care.</p>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"101474"},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873263","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":"Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets","authors":"Manuel Winkler ,&nbsp;Theresa Staniczek ,&nbsp;Maximilian Suhayda ,&nbsp;Sina Wietje Kürschner-Zacharias ,&nbsp;Johannes Hoffmann ,&nbsp;Julio Cordero ,&nbsp;Linda Kraske ,&nbsp;Hannah Maude ,&nbsp;Dorka Nagy ,&nbsp;Rita Manco ,&nbsp;Carsten Sticht ,&nbsp;Michelle Neßling ,&nbsp;Karsten Richter ,&nbsp;Gergana Dobreva ,&nbsp;Anna Maria Randi ,&nbsp;Inês Cebola ,&nbsp;Kai Schledzewski ,&nbsp;Philipp-Sebastian Reiners-Koch ,&nbsp;Sergij Goerdt ,&nbsp;Christian David Schmid","doi":"10.1016/j.jhepr.2025.101475","DOIUrl":"10.1016/j.jhepr.2025.101475","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Liver sinusoidal endothelial cells (LSECs) are highly specialized components of the hepatic vascular niche, regulating liver function and disease pathogenesis through angiocrine signaling. Recently, we identified GATA4 as a key transcription factor controlling LSEC development and protecting against liver fibrosis. As the transcription factor c-Maf was strongly downregulated in &lt;em&gt;Gata4&lt;/em&gt;-deficient LSECs, we hypothesized that c-Maf might be an important downstream effector of GATA4 in LSEC differentiation and liver fibrogenesis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Clec4g-iCre/Maf&lt;/em&gt;&lt;sup&gt;&lt;em&gt;fl/fl&lt;/em&gt;&lt;/sup&gt; (&lt;em&gt;Maf&lt;/em&gt;&lt;sup&gt;&lt;em&gt;LSEC-KO&lt;/em&gt;&lt;/sup&gt;) mice with LSEC-specific &lt;em&gt;Maf&lt;/em&gt; deficiency were generated and liver tissue was analyzed histologically. LSECs were isolated for bulk RNA-seq, ATAC-seq, and single-cell (sc) RNA-seq analysis. &lt;em&gt;Maf&lt;/em&gt;&lt;sup&gt;&lt;em&gt;LSEC-KO&lt;/em&gt;&lt;/sup&gt; livers were analyzed after MASH diet feeding. The expression of &lt;em&gt;MAF&lt;/em&gt; and its targets was analyzed in published human scRNA-seq data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Endothelial &lt;em&gt;Maf&lt;/em&gt; deficiency resulted in perisinusoidal liver fibrosis (Sirius red 0.46% &lt;em&gt;vs&lt;/em&gt;. 2.92%; &lt;em&gt;p&lt;/em&gt; &lt;0.05) without affecting metabolic liver zonation, accompanied by a switch from sinusoidal to continuous endothelial cell identity, which was aggravated upon MASH diet feeding (&lt;em&gt;p&lt;/em&gt; &lt;0.01). Furthermore, endothelial &lt;em&gt;Maf&lt;/em&gt; deficiency caused LSEC proliferation (&lt;em&gt;p &lt;&lt;/em&gt;0.05) and expression of profibrotic angiocrine factors including &lt;em&gt;Pdgfb&lt;/em&gt;, &lt;em&gt;Igfbp5&lt;/em&gt;, &lt;em&gt;Flrt2, and Cxcl12&lt;/em&gt;, among which FLRT2 (&lt;em&gt;p&lt;/em&gt; &lt;0.01) and CXCL12 (&lt;em&gt;p&lt;/em&gt; &lt;0.001) activated hepatic stellate cells &lt;em&gt;in vitro&lt;/em&gt;. scRNA-seq revealed replacement of zonated LSEC subpopulations with capillarized, proliferative, sprouting and secretory endothelial cell subsets that promote liver fibrogenesis and angiogenesis. This fundamental dysregulation of LSEC gene expression and differentiation was caused by changes in chromatin accessibility and transcription factor activity following loss of &lt;em&gt;Maf&lt;/em&gt;. Notably, endothelial &lt;em&gt;MAF&lt;/em&gt; expression was also significantly reduced in human cirrhotic livers (&lt;em&gt;p &lt;&lt;/em&gt;0.0001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Hepatic endothelial c-Maf protects against metabolic dysfunction-associated steatohepatitis-like liver fibrosis and regulates endothelial differentiation and zonation by controlling chromatin opening.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;This work builds on the known importance of liver sinusoidal endothelial cells in liver function and disease. Here, transcription factor c-Maf is identified as a master regulator in maintaining normal differentiation and zonation of liver sinusoidal endothelial cells, thereby protecting against the development of liver fibrosis/cirrhosis. The findings are significant for researchers and clinician","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"Article 101475"},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749587","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":"Attributable burden of steatotic liver disease on cardiovascular outcomes in Asia","authors":"Szu-Ching Yin ,&nbsp;Yi-Ting Chen ,&nbsp;Wei-Ting Chang ,&nbsp;Tzu-I Chen ,&nbsp;Tsai-Hsuan Yang ,&nbsp;Xia-Rong Liu ,&nbsp;Chia-Wei Huang ,&nbsp;Yu-Wei Chen ,&nbsp;Mei-Hsuan Lee","doi":"10.1016/j.jhepr.2025.101479","DOIUrl":"10.1016/j.jhepr.2025.101479","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;The associations between metabolic dysfunction-associated steatotic liver disease (MASLD) and specific cardiovascular events, as well as their attributable burdens, remain inconsistent and underexplored within a single population. This large-scale prospective cohort evaluated the associations between MASLD and various cardiovascular outcomes. Two additional steatotic liver disease (SLD) subtypes – MASLD with increased alcohol consumption (MetALD) and alcohol-related liver disease (ALD) – were also evaluated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We included 303,589 adults aged ≥30 years from Taiwan who underwent health examinations between 1997 and 2013. MASLD was defined by ultrasound-detected steatosis, limited alcohol intake, and ≥1 cardiometabolic risk factor. MetALD and ALD were defined based on alcohol intake thresholds and cardiometabolic profiles. Participants were followed until 2020, with outcomes and mortality ascertained via linkage to national registries. Cox proportional hazards models were used to estimate adjusted relative risks (RRs), and population attributable fractions (PAFs) were calculated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of the total population, 91,877 (30.3%) had MASLD, 7,490 (2.5%) had MetALD, 5,576 (1.8%) had ALD, and 198,646 (65.4%) did not have SLD. Over a median follow-up of 10.4 years, 162,959 cardiovascular events occurred. The adjusted RR of any cardiovascular diseases was 1.29 (95% CI 1.38-1.31) for MASLD, 1.38 (95% CI 1.34-1.42) for MetALD, and 1.48 (95% CI 1.43-1.53) for ALD. Among all SLD subtypes, MASLD showed the highest RR for myocardial infarction (RR 1.46, 95% CI 1.36–1.56). Findings remained consistent after accounting for liver-related deaths. The PAF for MASLD was 8.07% (95% CI 7.81–8.58). Despite higher risks, MetALD and ALD had lower PAFs due to lower prevalence.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;All major SLD subtypes – MASLD, MetALD, and ALD – were associated with increased long-term cardiovascular risk, underscoring the need for early detection and cardiometabolic risk management across the SLD spectrum.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;This large-scale study of 303,589 individuals demonstrates that metabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of cardiovascular diseases by at least 29%. Cardiovascular risk further escalates across SLD subtypes with higher levels of alcohol consumption. Notably, MASLD was associated with the highest risk of myocardial infarction among all SLD subtypes. By quantifying population burden, we found that 8.07% of cardiovascular events may be preventable through effective MASLD prevention strategies, highlighting the critical role of cardiometabolic risk management. These findings emphasize the need to integrate MASLD identification and prevention into broader cardiometabolic care and public health frameworks.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical trial number&lt;/h3&gt;&lt;div&gt;not","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"Article 101479"},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749593","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":"Impact of genetic variants linked to liver fat and liver volume on MRI-mapped body composition.","authors":"Shafqat Ahmad, Germán D Carrasquilla, Taro Langner, Uwe Menzel, Nouman Ahmad, Sergi Sayols-Baixeras, Koen F Dekkers, Beatrice Kennedy, Filip Malmberg, Ulf Hammar, María J Romero-Lado, Jenny C Censin, Diem Nguyen, Andrés Martínez Mora, Tuomas O Kilpeläinen, Lars Lind, Jan W Eriksson, Robin Strand, Joel Kullberg, Håkan Ahlström, Tove Fall","doi":"10.1016/j.jhepr.2025.101468","DOIUrl":"10.1016/j.jhepr.2025.101468","url":null,"abstract":"<p><strong>Background & aims: </strong>A quarter of the world population is estimated to have metabolic dysfunction-associated steatotic liver disease. Here, we aim to understand the impact of liver trait-associated genetic variants on fat content and tissue volume across organs and body compartments and on a large set of biomarkers.</p><p><strong>Methods: </strong>Genome-wide association analyses were performed on liver fat and liver volume estimated with magnetic resonance imaging in up to 27,243 unrelated European participants from the UK Biobank. Identified variants were assessed for associations with fat fraction and tissue volume in >2 million 'Imiomics' image elements in 22,261 individuals and with circulating biomarkers in 310,224 individuals.</p><p><strong>Results: </strong>We confirmed four liver fat and nine liver volume previously reported genetic variants (<i>p</i> values <5 × 10^-8). We further found evidence suggestive of a novel liver volume locus, <i>ADH4</i>, where each additional T allele increased liver volume by 0.05 SD (SE = 0.01, <i>p</i> value = 3.3 × 10^-8). The Imiomics analyses showed that liver fat-increasing variants were specifically associated with fat fraction of the liver tissue (<i>p</i> values <2.8 × 10^-3) and with higher inflammation, liver and renal injury biomarkers, and lower lipid levels. Associations of liver volume variants with fat content, tissue volume, and biomarkers were more heterogeneous, for example the liver volume-increasing alleles at <i>CENPW</i> and <i>PPP1R3B</i> were associated with higher skeletal muscle volumes and were more pronounced in men, whereas the <i>GCKR</i> variant was negatively associated with lower skeletal muscle volumes in women (<i>p</i> values <2.8 × 10^-3).</p><p><strong>Conclusions: </strong>Liver fat-increasing variants were mostly linked to fat fraction of the liver and were positively associated with some adverse metabolic biomarkers and negatively with lipids. In contrast, liver volume-associated variants showed a less consistent pattern across organs and biomarkers.</p><p><strong>Impact and implications: </strong>Liver fat and liver volume are common metabolic traits with a strong genetic component, yet the extent to which they exert organ-specific <i>vs.</i> systemic effects remains poorly defined. By integrating genome-wide association analyses and high-resolution neck-to-knee magnetic resonance imaging data through the Imiomics framework, this study reveals distinct genetic architectures for liver fat and liver volume, including sex-specific effects. These findings provide new insights into the biological, organ-level, tissue-specific, and systemic characteristics of steatotic liver disease and its genetic determinants. The results may inform the development of precision imaging genetic approaches, biomarker discovery, and stratified risk assessment strategies, while reinforcing the importance of incorporating sex-specifi","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 9","pages":"101468"},"PeriodicalIF":7.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873262","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":"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}