Liver International最新文献

{"title":"From Naltrexone Induction to Response-Guided Care in Alcohol-Associated Cirrhosis","authors":"Xiaoya Mao, Xujiao Hu","doi":"10.1111/liv.70872","DOIUrl":"10.1111/liv.70872","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Acetylation Activity of p300/CBP Ameliorates Hepatic Steatosis Through Downregulation of ACSL4","authors":"Ling-Yan Cai,&nbsp;Ya-Ping Guan,&nbsp;Jin-Han Hu,&nbsp;Chun-Yan Sun,&nbsp;Chen-Hong Ding,&nbsp;Xin Zhang,&nbsp;Xin Zeng,&nbsp;Wei-Fen Xie","doi":"10.1111/liv.70846","DOIUrl":"10.1111/liv.70846","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder, with few optimal pharmacotherapies. Ongoing studies are providing evidence that histone acetylation contributes to the progression of MASLD. This study investigated the alterations of specific histone acetylation sites in MASLD tissues and the effects of B029-2, a small-molecule inhibitor targeting p300/CBP acetylation activity, in mouse models of progressive fatty liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The acetylation of H3K27/H3K18/H3K9 was assessed in liver samples from MASLD patients and mice. The effect of the B029-2 in MASLD was assessed in MASLD models. A ChIP assay was conducted to investigate the epigenetic regulatory mechanism of ACSL4. Hepatic-specific Acsl4-knockout and overexpression mice were generated to validate the role of ACSL4 in MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed a significant increase in p300 HAT activity, p300/CBP-induced H3K18ac and H3K27ac levels in MASLD and B029-2 markedly reduced hepatic steatosis in vitro and in vivo. Transcriptome analysis revealed that B029-2 inhibited the expression of genes in the triglyceride biosynthetic process and long-chain fatty-acyl-CoA biosynthetic process. ChIP assay showed that H3K18ac, H3K27ac and p300 bind to the promoter region of <i>ACSL4</i>, and their binding is reduced by B029-2 treatment. AAV-mediated hepatic-specific overexpression of Acsl4 attenuated the effect of B029-2 on MASLD in mice, while hepatic-specific Acsl4-deficient in mice blocked the effect of B029-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>p300/CBP-mediated H3K18ac and H3K27ac regulate ACSL4-dependent lipid biosynthesis in MASLD and might be a potential therapeutic target for the treatment of MASLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next Generation Sequencing for the Differentiation of Benign and Malignant Biliary Strictures","authors":"Antonia Gillmeister,&nbsp;Julia Husman,&nbsp;Renate Schmelz,&nbsp;Stefan Brückner,&nbsp;Jochen Hampe,&nbsp;Daniela Aust,&nbsp;Sebastian Zeissig","doi":"10.1111/liv.70865","DOIUrl":"10.1111/liv.70865","url":null,"abstract":"<p>The differentiation between benign and malignant biliary strictures remains a significant clinical challenge. Recent studies have suggested that next generation sequencing (NGS) can improve the diagnostic accuracy. However, evidence on its performance in routine clinical practice is limited. Therefore, validation of the diagnostic value of NGS using real-world clinical data is warranted. We compared the performance of NGS analysis of cholangiocellular carcinoma (CCC)-associated mutations in endoscopic biopsies with that of histopathology, CA19-9 and cross-sectional imaging. NGS showed higher sensitivity for malignancy (65%) compared to histopathology (52%) at similar specificity (96% vs. 100%). The combination of NGS and histopathology further increased sensitivity for malignancy to 78% (<i>p</i> = 0.03) at similar specificity (96%). Our data provide support for the use of NGS in the diagnostic workup of biliary strictures.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Hepatitis C Virus Core Protein Induces Hepatic Steatosis Via Sirt1-Dependent Pathway’","authors":"","doi":"10.1111/liv.70852","DOIUrl":"10.1111/liv.70852","url":null,"abstract":"<p>\u0000 <span>C. Zhang</span>, <span>J. Wang</span>, <span>H. Zhang</span>, et al., “ <span>Hepatitis C Virus Core Protein Induces Hepatic Steatosis Via Sirt1-Dependent Pathway</span>,” <i>Liver International</i> <span>38</span>, no. <span>5</span> (<span>2018</span>): 803–812. https://doi.org/10.1111/liv.13581\u0000 </p><p>Each corrected strip was cropped directly from its corresponding original, uncropped Western blot image. The figure legends and all other elements of Figures 3B and 3D remain unchanged. No densitometric or statistical analyses were associated with the affected strips. The corrected images support the same interpretation described in the article and do not affect the Results, Discussion or conclusions.</p><p>We apologize for these errors.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcutaneous Fat Density Is an Independent Predictor of Adverse Outcomes and Shows Early Improvement After Liver Transplantation","authors":"Géraldine Dahlqvist,&nbsp;Salomé Declerck,&nbsp;Maxence Lepour,&nbsp;Alicia Delorme,&nbsp;Alix Collard,&nbsp;Pierre Trefois,&nbsp;Nicolas Lanthier","doi":"10.1111/liv.70862","DOIUrl":"10.1111/liv.70862","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Body composition is increasingly recognised as a prognostic determinant in cirrhosis, particularly in liver transplant (LT) candidates. We aimed to assess adipose and muscle compartments on computed tomography (CT) before and after LT and to evaluate their associations with mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited prospectively 121 patients with cirrhosis listed for LT. CT scans at the third lumbar vertebral level were analysed to quantify cross-sectional area (cm²) and density (Hounsfield units, HU) of skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue. A subset underwent a CT-scan 6 months post-LT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most patients were male (76%), and the median MELD score was 14 (IQR 10–20). High SAT density (&gt; −83 HU in women; &gt; −74 HU in men) was associated with higher pre-transplant mortality (<i>p</i> = 0.005) and with reduced overall survival during follow-up (<i>p</i> = 0.005) compared to lower SAT density. The combined phenotype of low muscle density and high SAT density identified the subgroup with the poorest survival (<i>p</i> = 0.002). From baseline to 6 months post-LT, SAT density decreased significantly (<i>p</i> = 0.0134), whereas muscle parameters did not change significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This prospective observational cohort study demonstrates that SAT density is a prognostic CT-derived marker in patients with cirrhosis awaiting LT with significant post-transplant dynamics. The impact of altered adipose tissue therefore warrants attention in this situation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis Drives TLR Ligand-Induced Maturation and Immune Activation of Liver Sinusoidal Endothelial Cells","authors":"Yiwen Shu,&nbsp;Hu Yan,&nbsp;Hang Sun,&nbsp;Xin Gu,&nbsp;Elisabeth Littwitz-Salomon,&nbsp;Jia Liu,&nbsp;Jun Wu,&nbsp;Dongliang Yang,&nbsp;Xin Zheng,&nbsp;Mengji Lu,&nbsp;Yanqin Du","doi":"10.1111/liv.70864","DOIUrl":"10.1111/liv.70864","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Liver sinusoidal endothelial cells (LSECs) are liver-resident antigen-presenting cells that induce immune tolerance, a feature exploited by persistent viruses. Toll-like receptor (TLR) ligands can override this tolerance, but whether metabolic reprogramming underlies LSEC activation remains unknown. We investigated whether TLR ligand-induced functional changes in LSECs require glycolysis and explored the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>LSECs from wild-type and chronic hepatitis B virus (HBV) replication mice were stimulated with TLR2 ligand P3C or TLR9 ligand ODN1826. LSEC maturation, cytokine production and T cell-priming capacity were assessed. Glycolytic flux was measured by metabolomics and Seahorse analysis. The glycolysis inhibitor 2-deoxy-D-glucose (2-DG) was used, and mTORC1 pathway involvement was examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The TLR2 ligand P3C promoted LSEC maturation, while the TLR9 ligand ODN1826 enhanced IL-12 production. Both ligands potentiated LSEC-induced T cell responses. In LSECs isolated from a mouse model of chronic HBV replication, P3C and ODN1826 also induced maturation and enhanced T cell-activating capacity, albeit to a weaker extent. Metabolomics and Seahorse analyses revealed that TLR2/9 ligands enhanced glycolysis and oxidative phosphorylation in LSECs, accompanied by activation of the mTORC1/HIF-1α/c-Myc axis. Blocking glycolysis with 2-DG significantly reduced co-stimulatory molecule expression on P3C-stimulated LSECs and IL-12 production by ODN1826-stimulated LSECs in both wild-type and chronic HBV models. Mechanistically, 2-DG suppressed the mTORC1 pathway, thereby attenuating TLR ligand-induced responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TLR ligand-induced activation and pro-inflammatory functions of LSECs critically depend on glycolysis via the mTORC1 signalling pathway. This reveals a key metabolic mechanism underlying LSEC immune regulation during innate stimulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: “Considerations on the Histologic Definition and Clinical Translation of Burnt-Out MASLD in Resected HCC”","authors":"Yukihiro Watanabe,&nbsp;Masayasu Aikawa,&nbsp;Kojun Okamoto,&nbsp;Isamu Koyama","doi":"10.1111/liv.70861","DOIUrl":"10.1111/liv.70861","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Season-Aware Aminotransferase Interpretation in Type 2 Diabetes: Response to Dai and Wang","authors":"Ryota Toki,&nbsp;Masaya Sakamoto","doi":"10.1111/liv.70851","DOIUrl":"10.1111/liv.70851","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 10","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Portal Vein Thrombosis Risk in Cirrhotic Patients With Portal Hypertension on Beta-Blockers: A Multi-Institutional Cohort Study.","authors":"Hazem Abosheaishaa, Khaled Elfert, Mohammed Abusuliman, Abdellatif Ismail, Abdullah Olimy, Ahmed Elsayed Alzamzamy, Ahmed Omran, Vincent Rizzo, Mahmoud Nassar, Mohamed El-Kassas","doi":"10.1111/liv.70843","DOIUrl":"10.1111/liv.70843","url":null,"abstract":"<p><strong>Background: </strong>Portal vein thrombosis (PVT) is a significant complication of cirrhosis. Nonselective beta-blockers (NSBBs) are standard therapy for portal hypertension, but their effect on PVT risk remains uncertain.</p><p><strong>Aim: </strong>To assess whether NSBB use after variceal band ligation increases PVT risk and to compare outcomes among propranolol, carvedilol and no NSBB therapy.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the TriNetX US Collaborative Network (> 110 million patients). Adults with cirrhosis and portal hypertension who underwent variceal band ligation (2010-2024) were included. Patients were stratified by NSBB exposure and matched 1:1 on 12 clinical variables. The primary outcome was incident PVT; secondary outcome was all-cause mortality. Kaplan-Meier analysis evaluated time-to-event outcomes.</p><p><strong>Results: </strong>After matching (n = 4296 per group), NSBB use was associated with higher PVT incidence compared with no NSBBs (9.5% vs. 5.4%; RR 1.765, 95% CI 1.500-2.077). Propranolol was associated with increased PVT risk, whereas carvedilol showed similar PVT incidence to controls and significantly lower mortality compared with both propranolol and no NSBB use.</p><p><strong>Conclusions: </strong>Propranolol use was linked to increased PVT risk, while carvedilol did not elevate PVT risk and was associated with improved survival. Beta-blocker selection may meaningfully influence outcomes in cirrhosis.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":"e70843"},"PeriodicalIF":6.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Differentiation of Nonperipheral Washout Refines Prognostic Stratification in HCC.","authors":"Yingyi Wu, Junhan Pan, Ting Yang, Hong Wei, Guzalinu Wufuer, Tianyi Xia, Yuanan Wu, Yanyan Zhang, Hui-Chuan Sun, Shenghong Ju, Feng Chen, Maxime Ronot, Bin Song, Hanyu Jiang, Yanshu Wang","doi":"10.1111/liv.70838","DOIUrl":"10.1111/liv.70838","url":null,"abstract":"<p><strong>Background and aims: </strong>Nonperipheral washout is a major imaging feature of hepatocellular carcinoma (HCC) with prognostic value, but whether its temporal differentiation can refine prognostic stratification remains understudied. This study aimed to investigate the prognostic implications of nonperipheral washout timing in HCC.</p><p><strong>Methods: </strong>This multicentre, retrospective cohort study included patients who underwent curative resection for single BCLC stage 0/A HCC and preoperative extracellular contrast agent-enhanced MRI at seven tertiary centres (March 2011 to April 2023). Three masked radiologists independently evaluated nonperipheral washout patterns, which were classified as early (present in the portal venous phase), late (present only in the delayed phase), or absent. Early recurrence-free survival (eRFS; ≤ 2 years) and 5-year RFS were assessed using Kaplan-Meier and Cox regression analyses.</p><p><strong>Results: </strong>A total of 611 patients (median age, 55 years; 520 men) were included. Early, late, and no washout were observed in 367 (60.1%), 95 (15.5%), and 149 (24.4%) patients, respectively. Inter- and intra-reader agreements were substantial to excellent (κ range, 0.67-0.94). Early washout was associated with microvascular invasion (p = 0.01) and Edmondson-Steiner G3/4 (p = 0.002). The eRFS rates were 67.3%, 82.1%, and 85.2% for the early, late, and no-washout groups (p < 0.001); the 5-year RFS rates were 53.4%, 62.1%, and 71.8% (p = 0.002). In multivariable Cox analysis adjusting for factors, early washout independently predicted eRFS (HR, 1.86; p < 0.001) and 5-year RFS (HR, 1.46; p = 0.006).</p><p><strong>Conclusions: </strong>In patients undergoing curative resection for single BCLC 0/A HCC, temporal differentiation of nonperipheral washout refines prognostic stratification, with early washout identifying patients at higher risk of recurrence.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"46 9","pages":"e70838"},"PeriodicalIF":6.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}