Annals of hepatology最新文献

{"title":"Is FIB-4 the right tool for screening for liver fibrosis?","authors":"Leen J.M. Heyens ,&nbsp;Demi P.A. van Malde ,&nbsp;Gediz Dogay Us ,&nbsp;Francesco Innocenti ,&nbsp;Mathieu Struyve ,&nbsp;Christophe Van Steenkiste ,&nbsp;Sven Francque ,&nbsp;Geert Robaeys ,&nbsp;Ger H. Koek","doi":"10.1016/j.aohep.2025.102176","DOIUrl":"10.1016/j.aohep.2025.102176","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>The screening accuracy of non-invasive fibrosis tests like FIB-4 in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Using standard cut-offs, this study evaluated FIB-4′s agreement with vibration-controlled transient elastography (VCTE) and identified and validated new thresholds.</div></div><div><h3>Patients and Methods</h3><div>A prospective cohort study (2019–2024) in Belgian and Dutch primary care used VCTE by FibroScan® (Echosens, France) as a proxy for the fibrosis stage. The FIB-4 index was derived from electronic patient data and study blood samples. Agreement between VCTE and FIB-4 was analysed using weighted Cohen’s kappa. New fibrosis cut-offs (≥F2; ≥8 kPa) for ≤65 and &gt;65 years were determined via Youden’s Index and validated in a Turkish primary care cohort and a Belgian secondary care T2DM cohort.</div></div><div><h3>Results</h3><div>Among 563 participants (median age 62 years, 47.1 % male, 14.2 % with T2DM, median BMI 28.2 kg/m²), FIB-4 showed poor agreement with VCTE (κ = 0.138, 95 % CI: 0.069–0.207). Suggested new cut-offs of 1.29 (≤65 years) and 1.72 (&gt;65 years) were proposed. The 1.29 cut-off performed similarly to the existing 1.3 in validation cohorts. In the Türkiye and T2DM cohorts, the 1.72 cut-off improved sensitivity over 2.0 but had lower specificity.</div></div><div><h3>Conclusions</h3><div>The FIB-4 index showed poor agreement with VCTE and low sensitivity, making it an unreliable standalone diagnostic tool for liver fibrosis in people with MASLD in both primary and secondary care. Alternative non-invasive tests or improved cut-off values are needed for accurate fibrosis detection in clinical practice.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"31 2","pages":"Article 102176"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of the HABIT score: a practical and robust tool to predict hepatic steatosis using HbA1c, BMI, and triglycerides in patients with unexplained elevated liver enzymes.","authors":"Eike Humbert, Verena Wilkens, Semjon Bugaichuk, Karoline Horvatits, Ansgar W Lohse, Samuel Huber, Sven Pischke, Thorben Fründt","doi":"10.1016/j.aohep.2026.102218","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102218","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Unexplained elevated liver enzymes (ELE) are common and often linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Diagnosis in primary care is difficult due to limited access to advanced imaging, highlighting the need for simple non-invasive tools. This study aimed to develop and validate a pragmatic, laboratory-based score to predict hepatic steatosis in patients with unexplained ELE.</p><p><strong>Patients and methods: </strong>A derivation cohort of 206 patients with 40 classified as steatosis-positive with a NAFLD Activity Score (NAS) ≥4 was analyzed. Candidate predictors were tested by univariate analysis and entered into multivariate logistic regression. Regression coefficients were scaled to construct an integer-based score (HABIT). Validation was performed in a retrospective cohort of patients with unexplained ELE attending our hepatology clinic between 2019 and 2021(n = 648), all undergoing standardized diagnostic work-up including ultrasound, elastography, and laboratory testing.</p><p><strong>Results: </strong>Multivariate analysis identified HbA1c, body mass index (BMI), and triglycerides as independent predictors of steatosis. The HABIT score was derived as: (61 × HbA1c [%]) + (3 × BMI [kg/m²]) + Triglycerides [mg/dL]. Diagnostic accuracy was high in the derivation cohort (AUROC: 0.83) and robust in validation (AUROC: 0.81), outperforming the Hepatic Steatosis Index (HSI, AUROC: 0.77). Cut-offs <490 and >630 reliably ruled out (sensitivity 93.6%) or confirmed (specificity 92.5%) steatosis. Score values correlated significantly with ultrasound grades and CAP.</p><p><strong>Conclusions: </strong>The HABIT score is a simple, robust tool for identifying hepatic steatosis in unexplained ELE. It outperforms HSI and may facilitate early detection and risk stratification in primary care with limited diagnostic resources.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102218"},"PeriodicalIF":4.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of frailty with cardiovascular diseases and mortality in metabolic dysfunction-associated steatotic liver disease.","authors":"Fuyi Ma, Huanyu Wang, Kang Wan, Yuan Li, Yuhang Chen, Ru Wang","doi":"10.1016/j.aohep.2026.102214","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102214","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Frailty is highly prevalent in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the extent to which frailty influences cardiovascular disease (CVD) incidence, cardiovascular mortality, and all-cause mortality in MASLD individuals remains poorly understood. This study aimed to evaluate the impact of frailty on cardiovascular outcomes and mortality in this population.</p><p><strong>Patients and methods: </strong>A total of 193,942 participants without prior CVD from the UK Biobank were included. Participants were categorized into three groups based on frailty phenotype: non-frailty, pre-frailty, and frailty. MASLD was defined as hepatic steatosis accompanied by at least one cardiometabolic abnormality. The primary outcome was CVD incidence, with secondary outcomes including cardiovascular and all-cause mortality.</p><p><strong>Results: </strong>After multivariate adjustment, the risk of CVD was higher in MASLD participants with pre-frailty (HR 1.08, 95% CI 1.05-1.12) and frailty (HR 1.41, 95% CI 1.33-1.49) than in those with non-frailty. The association of frailty with CVD was strongest in participants with MASLD and advanced fibrosis (HR 2.60, 95% CI 2.04-3.30), intermediate in MASLD without fibrosis (HR 1.73, 95% CI 1.63-1.84), and weakest in non-MASLD (HR 1.58, 95% CI 1.47-1.70). Similar results were also observed for cardiovascular mortality. Furthermore, among the five components of frailty phenotype, slow gait speed demonstrated the strongest associations with the risks of CVD incidence in MASLD, cardiovascular mortality, and all-cause mortality.</p><p><strong>Conclusions: </strong>Frailty was associated with increased risks of CVD incidence, cardiovascular mortality, and all-cause mortality among individuals with MASLD, particularly those with a higher fibrosis burden as defined by FIB-4.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102214"},"PeriodicalIF":4.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Serum IL-6 is a prognostic biomarker for advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab\".","authors":"Ningbo Xiao, Jinliang Dong, Qiujing Wang","doi":"10.1016/j.aohep.2026.102215","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102215","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102215"},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital twin frameworks for Hepatitis C: Toward predictive, and personalised management.","authors":"Ruqaiyyah Siddiqui, Naveed Ahmed Khan","doi":"10.1016/j.aohep.2026.102216","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102216","url":null,"abstract":"<p><p>Despite the availability of antivirals, Hepatitis C remains a major global public health challenge, with over 50 million people living with chronic infection and many remaining undiagnosed or untreated. Transmission persists in marginalised populations, reinfection occurs in high-risk groups, and long-term complications including cirrhosis and hepatocellular carcinoma continue to drive morbidity and mortality. Disease progression, treatment response, and transmission risk are highly heterogeneous and dynamic, shaped by host genetics, immune status, viral kinetics, comorbidities, behavioural exposures, and health-system access. Digital twin, defined as adaptive computational models that continuously mirror an individual's biological and clinical state, offers a transformative approach for predictive and personalised Hepatitis C care. By integrating virological, immunological, biochemical, behavioural, and environmental data, digital twins could enable real-time forecasting of disease progression, optimisation of antiviral therapy, early detection of treatment failure or reinfection, and precision targeting of public-health interventions. This article outlines a conceptual framework for constructing digital twins for Hepatitis C, discusses clinical and population-level applications, and examines the ethical, technical, and translational challenges that must be addressed to support global elimination strategies.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102216"},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesencephalic astrocyte-derived neurotrophic factor (MANF): a context-dependent therapeutic regulator and potential biomarker in liver diseases.","authors":"Yu Liu, Hao-Wen Wang, Li-Jun Zhang, Tong Zhu, Min Xue, Yu-Xian Shen, Li-Jie Feng","doi":"10.1016/j.aohep.2026.102217","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102217","url":null,"abstract":"<p><p>Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a highly conserved protein that plays crucial roles in cellular stress responses and exerts profound impacts on multiple diseases. Accumulating evidence demonstrates that MANF is involved in various liver pathological conditions, including hepatocellular carcinoma (HCC), liver fibrosis, liver regeneration, lipid metabolism dysregulation, and drug-induced liver injury. Notably, the functions of MANF extend beyond the liver itself; it can systemically regulate the progression of liver diseases by coordinating liver-multiorgan crosstalk, such as the gut-liver and spleen-liver axes. Furthermore, its regulatory actions exhibit diverse and context-dependent patterns, which are tightly coupled to the specific cell type and disease setting. Therefore, MANF is not only a key molecule for understanding the mechanisms underlying liver diseases but also a potential systemic modulator in the liver-associated metabolic-immune network. This review aims to systematically elucidate the expression, functions, and multi-organ interactive mechanisms of MANF in liver diseases, and to assess the evidence supporting its pathophysiological and contingent therapeutic relevance.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102217"},"PeriodicalIF":4.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibulin-3 as a reliable biomarker of fibrosis in obese subjects with metabolic dysfunction-associated steatotic liver disease.","authors":"Allen Anthony Laraño, Silvia Palmisano, Deborah Bonazza, Discipio Marina, Marica Meroni, Anna Ludovica Fracanzani, Lory S Crocè, Claudio Tiribelli, Paola Dongiovanni, Natalia Rosso, Pablo Giraudi","doi":"10.1016/j.aohep.2026.102206","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102206","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about one-quarter of adults worldwide, and liver fibrosis is its strongest predictor of liver-related morbidity and mortality. Using combined in-silico screening and experimental evaluation, we aimed to identify circulating biomarkers associated with fibrosis progression. Fibulin-3 was identified, and its diagnostic performance was evaluated in biopsy-proven MASLD cohorts.</p><p><strong>Materials and methods: </strong>The GSE125251 RNA-seq dataset was reanalyzed to compare liver transcriptomes from MASLD subjects with minimal (F0-F1) versus moderate to advanced fibrosis (F2/F3-F4). Differentially expressed genes (DEGs) were filtered to retain plasma-secreted, protein-coding candidates. Top-ranked genes were evaluated in liver biopsies from a morbidly obese cohort (n = 65) stratified by fibrosis stage, and their plasma levels were measured via ELISA in two independent bariatric cohorts (combined n = 225).</p><p><strong>Results: </strong>Among 106 DEGs, 22 encoded plasma-circulating proteins. Six top candidates (EFEMP1, LTBP2, LUM, DPT, CHI3L1, CCL20) were prioritized. EFEMP1 (Fibulin-3) showed the strongest association with fibrosis, with significantly higher hepatic mRNA and protein expression in F2/F3-F4 versus F0-F1 (p < 0.005). Plasma Fibulin-3 levels correlated with fibrosis stage (ρ=0.40, p < 0.0001), increasing from 9.4 ng/mL in F0-F1 to 21.7 ng/mL in F2/F3-F4. Its diagnostic performance for F ≥ 2 (AUROC = 0.78) exceeded that of APRI, FIB-4, NFS, and HSI. A combined index including Fibulin-3, HSI, platelets, and GGT increased the AUROC to 0.87 (CI: 0.79-0.92).</p><p><strong>Conclusions: </strong>Plasma Fibulin-3 is notably higher in individuals with advanced MASLD and represents a promising non-invasive biomarker for liver fibrosis stratification in metabolically unhealthy obese populations.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102206"},"PeriodicalIF":4.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global academic hepatology capacity index (IGCAH): a multi-source assessment reveals profound inequities across Latin America.","authors":"Pablo Coste, Ezequiel Ridruejo, Luis Antonio Díaz, Juan Pablo Arab, Mario Pessoa, Nelia Hernández, Marco Arrese","doi":"10.1016/j.aohep.2026.102211","DOIUrl":"https://doi.org/10.1016/j.aohep.2026.102211","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Academic hepatology capacity in Latin America is highly heterogeneous, yet no standardized regional framework exists to quantify structural differences across countries. We aimed to develop and apply the Global Academic Hepatology Capacity Index (IGCAH), a composite metric integrating academic, clinical, and research dimensions, to characterize cross-country inequities in the region.</p><p><strong>Materials and methods: </strong>National hepatology societies from 20 Latin American countries completed a 54-item structured survey. Five domain indices: human capacity, academic training, scientific productivity, clinical complexity, and collaboration/networking, were constructed using standardized z-scores and integrated into the IGCAH. Findings were triangulated with bibliometric analysis of PubMed-indexed hepatology publications (2015-2025) and thematic analysis of abstracts submitted to the ALEH 2025 Congress.</p><p><strong>Results: </strong>Complete responses were obtained from all 20 countries. The five highest-performing countries concentrated over 80% of the hepatology workforce, formal training programs, research infrastructure, and access to advanced therapies (IGCAH >0.8). Overall, 55% of countries lacked formal specialty recognition, 45% reported absence of essential laboratory infrastructure, and only 50% met criteria for sufficient diagnostic and therapeutic complexity. Clinical services were centralized in ≤2 major cities in 70% of countries, and ten reported ≤2 national liver disease registries. Scientific productivity was highly concentrated, with four countries accounting for approximately 85% of PubMed-indexed hepatology publications, while more than half produced ≤5 papers annually. ALEH 2025 abstracts mirrored these disparities, with 75% originating from five countries; most were observational and clinical trials were scarce.</p><p><strong>Conclusions: </strong>Profound asymmetries characterize academic hepatology in Latin America. The IGCAH provides a robust framework to identify structural gaps and guide targeted, stage-specific capacity strengthening.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102211"},"PeriodicalIF":4.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Making metabolic dysfunction-associated steatotic liver disease medicines affordable: Lessons from hepatitis C.","authors":"Khalid M AlNaamani, Mohamed El-Kassas, Zobair M Younossi","doi":"10.1016/j.aohep.2026.102213","DOIUrl":"10.1016/j.aohep.2026.102213","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102213"},"PeriodicalIF":4.4,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term antiviral therapy sustains HBsAg decline, increases HBV RNA negativity and enhances the proportion of patients achieving functional cure in chronic hepatitis B.","authors":"Ruihan Gao, Shuting Liu, Shiyu Zhang, Xin Zhou, Bin Zhu, Baoju Wang","doi":"10.1016/j.aohep.2026.102212","DOIUrl":"10.1016/j.aohep.2026.102212","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"102212"},"PeriodicalIF":4.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}