Hepatology Communications最新文献

{"title":"Reply: \"Physical frailty is the most important predictor of early mortality in hospitalized patients with decompensated cirrhosis\".","authors":"Francesca D'Arcangelo, Alberto Zanetto","doi":"10.1097/HC9.0000000000001041","DOIUrl":"10.1097/HC9.0000000000001041","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863805","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":"HLA and non-HLA genetic analyses reveal suggestive variants associated with statin-induced liver injury.","authors":"Callie Jo Zaborenko, Tae-Hwi Schwantes-An, Yi-Ju Li, Andrew Dellinger, Paola Nicoletti, Ann K Daly, Guruprasad Aithal, Naga Chalasani","doi":"10.1097/HC9.0000000000001026","DOIUrl":"10.1097/HC9.0000000000001026","url":null,"abstract":"<p><strong>Background: </strong>Statins are widely prescribed for cardiovascular risk reduction and are generally well tolerated. However, they can cause drug-induced liver injury (DILI), and the genetic factors contributing to statin-DILI remain poorly understood.</p><p><strong>Methods: </strong>HLA association and genome-wide association (GWAS) studies were conducted to identify genetic variants associated with statin-DILI. High-confidence cases (n=71) were identified from the Drug-Induced Liver Injury Network (DILIN) and compared with statin-exposed controls without liver injury (n=551) from the Indiana Biobank. Association testing was performed across ancestries and within ancestry, adjusting for age, sex, and three principal components of genotypes. Top variants were further evaluated in non-statin DILI cases and unexposed controls. In addition, we investigated the frequency of candidate variants among a comprehensive list of pharmacogenetic variants related to statins.</p><p><strong>Results: </strong>HLA-DQA1*03:01 was significantly associated with increased risk of statin-DILI (OR=3.49, 95% CI 2.21-5.51, p-value=1.27×10-7), with enrichment observed across multiple ancestry groups, particularly non-Hispanic Black and Hispanic individuals. From the GWAS, three loci showed suggestive associations (p-value <5×10-06) with statin-DILI, including rs35197737 in RGS1 (OR=5.03, 95% CI 1.11-3.66, p=1.14×10-7), rs75629598 in FRMD4A (OR=4.4, 95% CI=2.33-8.12, p=3.97×10-6), and rs7658630 in the intergenic region on chromosome 4 (OR=4.86, 95% CI 2.66-8.85, p=2.68×10-7). No pharmacogenetic variants revealed statistical significance.</p><p><strong>Conclusion: </strong>We identified HLA and non-HLA genetic variants associated with statin DILI. Future studies with larger sample sizes should confirm these observations.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880043","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":"A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.","authors":"Wen-Juei Jeng, Chi-Jen Chu, Apinya Leerapun, Anchalee Avihingsanon, Stefan Zeuzem, Stefan Bourgeois, Man-Fung Yuen, Manuel Romero-Gomez, Sheng-Shun Yang, Cristina Cravcenco, Bruno Salaun, Meng Shi, Ventzislav Vassilev, Joon Hyung Kim, Kristien Swinnen","doi":"10.1097/HC9.0000000000001025","DOIUrl":"10.1097/HC9.0000000000001025","url":null,"abstract":"<p><strong>Background: </strong>This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B).</p><p><strong>Methods: </strong>This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated.</p><p><strong>Results: </strong>In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors.</p><p><strong>Conclusions: </strong>Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792469","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":"The INTEGRATE prospective cohort study: Design and methods to evaluate biopsychosocial determinants of outcomes in early liver transplantation for alcohol-associated liver disease.","authors":"Lisa B VanWagner, Katherine M Keyes, MinJae Lee, David S Goldberg, Natasha Schaefer Solle, Anne C Fernandez, Jessica L Mellinger, Elizabeth C Verna","doi":"10.1097/HC9.0000000000001031","DOIUrl":"10.1097/HC9.0000000000001031","url":null,"abstract":"<p><strong>Background and aims: </strong>Early liver transplantation (eLT) for alcohol-associated liver disease (ALD), defined as transplant evaluation with <6 months of alcohol abstinence, is a life-saving therapy for select patients. However, critical gaps remain in understanding patient selection, management strategies, and longitudinal outcomes. To address these gaps, the multi-disciplinary INTEGRATE Collaborative was established to conduct 5 parallel studies using a mixed-methods research approach to comprehensively address these gaps. This manuscript describes the design and methods of the INTEGRATE cohort study, which aims to identify the biopsychosocial factors causally related to and predictive of stakeholder-relevant outcomes.</p><p><strong>Methods and results: </strong>The INTEGRATE cohort study is a prospective multicenter, longitudinal, observational study enrolling up to 680 adults with ALD undergoing evaluation for eLT at 4 U.S. centers. Participants are followed from transplant evaluation initiation through key pre-transplant and post-transplant milestones, with planned outcome surveillance for a minimum of 36 months, and longer as data are available. Data collection includes detailed alcohol use assessments, psychosocial and behavioral measures, clinical data, imaging, and biospecimen banking. The cohort is designed to identify biopsychosocial factors associated with and predictive of survival, waitlisting, alcohol-associated outcomes, healthcare utilization, and post-transplant clinical and patient-reported outcomes.</p><p><strong>Conclusions: </strong>The prospective INTEGRATE cohort study provides a rigorous observational foundation to inform patient selection, management, and outcome prediction in eLT for ALD. This method's manuscript details the cohort design to promote transparency, reproducibility, and integration with complementary INTEGRATE studies.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792470","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":"Effects of diabetes, obesity, and metabolic syndrome on alcohol-associated liver disease: A systematic review.","authors":"Dhiraj K Peddu, Vitchapong Prasitsumrit, Matthew J Kubina, Abhijay Kumar, Jasnoor Singh, Pojsakorn Danpanichkul, Matthew C Roslund, Suthat Liangpunsakul, Jessica L Mellinger, Karn Wijarnpreecha, Ponni V Perumalswami, Vincent L Chen","doi":"10.1097/HC9.0000000000001029","DOIUrl":"10.1097/HC9.0000000000001029","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-associated liver disease (ALD) is a leading cause of advanced liver disease and liver transplantation worldwide. Cardiometabolic risk factors (CMRFs) may worsen ALD prognosis. While recent nomenclature acknowledges the impact of CMRFs in steatotic liver disease with low-to-moderate alcohol use, individuals with high alcohol intake are still classified as having ALD regardless of CMRF status. We conducted a systematic review to evaluate the impact of CMRFs, primarily diabetes, obesity, and metabolic syndrome, on clinical outcomes in patients with ALD.</p><p><strong>Methods: </strong>We performed a systematic review of peer-reviewed studies published through October 21, 2025, as well as abstracts from the AASLD, EASL, DDW, ACG, and APASL conferences from 2023 to 2025. We included studies involving adults (≥18 y) with ALD that assessed at least one CMRF (eg, diabetes, obesity, metabolic syndrome) and reported longitudinal clinical outcomes. Primary outcomes included incident cirrhosis, hepatocellular carcinoma (HCC), overall and cause-specific mortality, cardiovascular events, liver-related complications, and liver transplantation.</p><p><strong>Results: </strong>Nineteen studies comprising 132,054 patients with ALD met the inclusion criteria. Diabetes was consistently associated with increased risks of overall mortality [adjusted hazard ratio (aHR) 3.00], liver-related mortality (aHR 3.60), HCC (hazard ratios 1.6-21.7), and cardiovascular mortality (aHR 19.91). Elevated BMI was linked to higher all-cause mortality (aHR 1.16-1.58), cardiovascular mortality (aHR 3.76), HCC incidence (HR 2.0-2.9), and liver-related mortality (aHR 16.22). Metabolic syndrome was associated with increased overall (HR 1.27-2.37) and liver-related mortality (HR 1.47-2.06). A greater burden of CMRFs was correlated with lower transplant-free survival and reduced rates of hepatic recompensation.</p><p><strong>Conclusion: </strong>Diabetes, obesity, and metabolic syndrome are associated with worse hepatic and extrahepatic outcomes in ALD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792531","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":"The rate of and risk factors for falls among patients with cirrhosis: A multicenter study.","authors":"Joy E Obayemi, Mitchell Paukner, Bima J Hasjim, Dominic Vitello, Paola A Barrios, Saad Hussain, Salva Balbale, Lisa B VanWagner, Mohsen Mohammadi, Sanjay Mehrotra, Oriana Dentici, Lihui Zhao, Daniela P Ladner","doi":"10.1097/HC9.0000000000001019","DOIUrl":"10.1097/HC9.0000000000001019","url":null,"abstract":"<p><strong>Background: </strong>Falls are associated with frailty and are a significant cause of morbidity among the elderly. Due to accelerated physiologic aging, frailty is common among patients with cirrhosis. We sought to identify the patients with cirrhosis at highest risk of falling and to explore the relationship between falls and frailty in this population.</p><p><strong>Methods: </strong>We conducted a longitudinal, retrospective analysis of adults (above 18 y old) with cirrhosis from 2011 to 2021 in the multi-institutional CAPriCORN database. Falls were defined by validated International Classification of Diseases 9th and 10th edition codes. Frailty was defined using the Hospital Risk Frailty Score (mild <5, intermediate 5-15, severe >5). Multivariable Cox models identified risk factors for experiencing a first and second fall (HR: 95% CI).</p><p><strong>Results: </strong>In total, 42,046 patients with cirrhosis were included with a median (IQR) age of 59.3 years (51.4-66.9) and mean (IQR) follow-up of 3.4 years (0.6-5.7). In total, 58.0% were male (n=24,390) and 59.5% had baseline compensated cirrhosis (n=25,021). Overall, 7.1% (n=2997) experienced a fall within the study period, 2.6% within 1 year of cirrhosis diagnosis. Prior fall history (HR: 5.69, 4.93-6.58), severe frailty (HR: 2.37, 2.02-2.80), and intermediate frailty (HR: 1.71, 1.49-1.96) were the strongest fall risk factors. In total, 38.4% of patients who fell experienced an additional fall during follow-up, 35% of which occurred within 1 year. Fall history (HR: 1.50, 1.18-1.90) and severe frailty (HR: 1.51, 1.16-1.96) were the strongest risk factors for a second fall. Patients with severe frailty had a 10-year cumulative fall incidence of 19.6%.</p><p><strong>Conclusions: </strong>Though 7% of patients experienced a fall, patients with a fall history or frailty were at significantly increased risk. These findings may help target patients with the highest fall risk and design fall-prevention interventions for this uniquely vulnerable population.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792490","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":"Challenges in the care of rare vascular liver diseases: Insights from patients, health care providers, and patient organizations.","authors":"Mercedes Guilabert, Agnes Dumas, Eva Gil-Hernández, Lynda Sifer-Rivière, Jane Sattoe, Guenda Bernegger, Maria Caiata Zufferey, María Purificación Ballester, Giada Danesi, Virginia Hernandez-Gea, Sarwa Darwish Murad, Pierre-Emmanuel Rautou, Laure Elkrief, Benedetta Terziroli Beretta-Piccoli, Andrea De Gottardi, Annalisa Berzigotti, Aurelie Plessier, José Joaquín Mira","doi":"10.1097/HC9.0000000000000998","DOIUrl":"10.1097/HC9.0000000000000998","url":null,"abstract":"<p><strong>Background: </strong>Patients with rare vascular liver diseases (VLDs), including non-cirrhotic portal vein thrombosis and Budd-Chiari syndrome, may develop severe complications from an early age. Yet, little is known about their healthcare experience and unmet needs. This study aimed to identify key challenges in the care of these patients across 4 European countries.</p><p><strong>Methods: </strong>Semi-structured interviews were conducted with patients, members of patient advocacy organizations (PAOs), and health care providers (HCPs) from France, Spain, Switzerland, and the Netherlands. A standardized interview guide explored challenges and unmet needs in healthcare. Using thematic framework analysis, themes were first identified nationally, then synthesized internationally.</p><p><strong>Results: </strong>Thirty-seven individuals participated: 13 patients, 7 PAO representatives, and 17 HCPs. Across countries, VLDs were seen as difficult to diagnose, communicate, and manage, given the uncertainty about their etiology, progression, and treatment. Four core challenges were identified: (1) diagnostic wandering, sometimes due to insufficiently targeted imaging requests and limited radiologic experience; (2) challenges in communicating the diagnosis given the complexity and severity of the disease; (3) scientific uncertainty regarding the etiology, progression, and treatment of VLDs, leading to difficulties for HCPs in risk interpretation and for patients in understanding and managing their condition; (4) challenges in care coordination, particularly for patients with associated diseases or comorbidities. In addition, supportive care, particularly in addressing mental health issues and fatigue, was considered insufficient, and management of reproductive and sexual health was considered to require tailored communication strategies.</p><p><strong>Conclusions: </strong>This study highlights perceived cross-country challenges in the care of patients with rare VLDs, underscoring the need for targeted interventions in communication and care coordination to improve their healthcare experience and outcomes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 9","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689269","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":"High incidence of advanced liver disease and mortality in patients presenting with alcohol use disorder.","authors":"Amir Gougol, Dhiraj Yadav, Robert Feldman, Andrew Althouse, Melissa Saul, Ana Clemente-Sanchez, Gavin Arteel, Ramon Bataller","doi":"10.1097/HC9.0000000000000979","DOIUrl":"10.1097/HC9.0000000000000979","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the long-term risk of developing cirrhosis in patients with alcohol use disorder (AUD).</p><p><strong>Methods: </strong>This was a retrospective cohort of patients with AUD presenting to healthcare centers between January 2006 and June 2017. Individuals ≥18 years old with a diagnosis of AUD based on ICD-9 and ICD-10 codes were included. Patients with concurrent cirrhosis were excluded. Then, patients were followed until August 2021 for the development of complications or mortality.</p><p><strong>Results: </strong>A total of 32,808 patients with AUD were included in the final analysis. During an average follow-up of 5.7 years, 12.3% of patients developed incident cirrhosis, and the overall mortality was 20.2%. The risk of cirrhosis increased in patients with diabetes mellitus (DM) [hazard ratio (HR), 1.52; 95% CI, 1.41-1.63; p<0.001] and hepatitis C (HR, 3.15; 95% CI, 2.93-3.39; p<0.001), whereas African American (AA) race had a protective effect (HR, 0.76; 95% CI, 0.7-0.82; p<0.001). Development of cirrhosis doubled the mortality rate (HR, 2.55; 95% CI, 2.39-2.72; p<0.001). The presence of DM, concomitant hepatitis C infection, and non-AA race collectively conferred a greater risk of cirrhosis and mortality in individuals with AUD.</p><p><strong>Interpretation: </strong>Patients presenting with AUD are at high risk for developing incident cirrhosis and mortality. Concurrent DM and hepatitis C increase the risk of cirrhosis and mortality. Early intervention in patients presenting with AUD is urgently warranted.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619538","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":"Global multicenter validation of noninvasive fibrosis assessment pathways in MetALD and ALD.","authors":"Hyundam Gu, Luis Antonio Díaz, Natalia Baeza, Francisco Idalsoaga, Xiao-Dong Zhou, Ming-Hua Zheng, Rakhi Maiwall, Shiv K Sarin, Anand V Kulkarni, Ramagundam Ramyasri, Fátima Higuera de la Tijera, Helena Cortez Pinto, Sofia Carvalhana, Rita Fernandes, Mohammad Qasim Khan, William Alazawi, Wenhao Li, Laura Temperley, David Marti-Aguado, Jordi Gratacós-Ginès, Elisa Pose, Maria Poca, Berta Cuyas, Pedro Montes, Fernando Javier Barreyro, Gustavo Ayares, Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Jimmy Che-To Lai, Cristiane Villela-Nogueira, Nathalie Leite, Gil Fernando Salles, Claudia Regina Lopes Cardoso, Daniza Contreras, José Antonio Velarde-Ruiz Velasco, Alceo Galimberti, Fernando Bessone, Francisco Javier Valentin-Cortez, Alejandra Mijangos-Trejo, Norberto C Chavez-Tapia, Ezequiel Ridruejo, Mirta Peralta, Juan Pablo Roblero, Daniela Simian, Pamela Gil, Mohamed El-Kassas, Angelo Z Mattos, Johana Acuña, Roberta Chaves Araujo, Igor Lima Ferraz, Katherine Marrugo, Alonso Vera Torres, Juan Diego Torres, Valentina Mejía Valdés, Jacqueline Córdova, Manuel Mendizabal, Claudia Alves Couto, Guilherme Grossi Lopes Cançado, Thomas G Cotter, Ahmad Anouti, Elias D Rady, Hamza Dahshi, Sheel Patel, Ashwani K Singal, Katrina Pekarska, Richard Parker, Mohamad Ali Ibrahim, Prasun K Jalal, Graciela Castro-Narro, Mazen Noureddin, Naim Alkhouri, Winston Dunn, Patrick S Kamath, Arun Sanyal, Richard K Sterling, Veeral Ajmera, Rohit Loomba, Marco Arrese, Ramón Bataller, Juan Pablo Arab","doi":"10.1097/HC9.0000000000001020","DOIUrl":"10.1097/HC9.0000000000001020","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive tests are well validated in metabolic dysfunction-associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test-based clinical care pathways for fibrosis risk stratification in MetALD and ALD.</p><p><strong>Methods: </strong>This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013-2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC.</p><p><strong>Results: </strong>Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0-61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD).</p><p><strong>Conclusions: </strong>In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602322","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":"The risk of cardiovascular events in metabolic dysfunction-associated steatotic liver disease according to fibrosis stage and diabetes status: A cohort study.","authors":"Jaehong Jeong, Jung Pyo Hong, Dong Yun Kim, Jae Seung Lee, Mi Na Kim, Jeong Eun Song, Hyun Chin Cho, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Hye Won Lee, Seung Up Kim","doi":"10.1097/HC9.0000000000001013","DOIUrl":"10.1097/HC9.0000000000001013","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated whether fibrosis severity assessed using guideline-recommended noninvasive liver fibrosis pathways was associated with incident ASCVD across different glycemic states.</p><p><strong>Methods: </strong>This retrospective cohort study included subjects with MASLD. Fibrosis severity was classified using the Korean Association for the Study of the Liver/European Association for the Study of the Liver (KASL/EASL) and American Gastroenterological Association (AGA) sequential pathways, based on fibrosis-4 followed by vibration-controlled transient elastography. Incident ASCVD was analyzed using Fine-Gray subdistribution hazard models, with death treated as a competing event.</p><p><strong>Results: </strong>Among 6519 subjects with MASLD who had both fibrosis-4 and vibration-controlled transient elastography data, 3243 had normoglycemia, 2369 had prediabetes, and 907 had diabetes; 3221 were included in the survival analysis cohort. Baseline 10-year ASCVD risk increased with worsening glycemic status. In the longitudinal analysis, the association between fibrosis severity and incident ASCVD differed by glycemic status. In patients with prediabetes, the highest fibrosis tier was associated with higher incident ASCVD risk (adjusted subdistribution hazard ratio: 2.62, p=0.024). This association was also more apparent in younger individuals. In patients with diabetes, 5-year cumulative ASCVD incidence was high across fibrosis tiers (15.2%-18.5%), without a significant increase by fibrosis severity.</p><p><strong>Conclusions: </strong>Higher liver fibrosis severity assessed by noninvasive tests was associated with incident ASCVD outcomes in selected MASLD subgroups, particularly patients with prediabetes and younger individuals. Fibrosis assessment may help identify patients who warrant closer cardiometabolic evaluation when interpreted alongside established ASCVD risk prediction tools.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602358","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}