Hepatology International最新文献

{"title":"Comparative risk of hepatocellular carcinoma and mortality among initiators of GLP-1 receptor agonists versus other glucose-lowering therapies: a target trial emulation.","authors":"Jesus Gibran Hernández-Pérez, Omer Abdelgadir, Subin Jang, Deepali K Ernest, Xiaotao Zhang, Dimpy Shah, Arthur S Hong, Jaime P Almandoz, Lindsay G Cowell, Sarah E Messiah, David S Lopez","doi":"10.1007/s12072-026-11138-9","DOIUrl":"10.1007/s12072-026-11138-9","url":null,"abstract":"<p><strong>Introduction: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1 RA) may influence pathways involved in hepatocarcinogenesis, but evidence regarding their association with hepatocellular carcinoma (HCC) and mortality risk remains heterogeneous. We evaluated the association between GLP-1 RA initiation and HCC incidence compared with commonly used glucose-lowering medications, with secondary exploratory analyses of all-cause mortality following HCC diagnosis.</p><p><strong>Methods: </strong>We emulated active-comparator, new-user target trials using Patient-Centered Clinical Research Network data from UT Southwestern Medical Center (PCORnet-UTSW; 2010-2025). Adults with T2D initiating GLP-1 RA were compared with initiators of metformin, insulin, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), and sulfonylureas. The primary outcome was incident HCC; a secondary analysis evaluated all-cause mortality after HCC diagnosis. Five-year risks and risk differences under the intention-to-treat (ITT) approach were estimated using pooled logistic regression with inverse probability of treatment weighting. Per-protocol analyses accounted for treatment adherence using inverse probability of censoring weights.</p><p><strong>Results: </strong>GLP-1 RA initiators had lower five-year HCC risk than comparator groups. Under ITT, risk differences were - 0.37% (95% CI - 0.59 to - 0.08) versus metformin, - 0.52% (95% CI - 0.74 to - 0.35) versus insulin, - 0.37% (95% CI - 0.70 to - 0.06) versus DPP4i, and - 0.39% (95% CI - 0.64 to - 0.13) versus sulfonylureas. Findings were stronger in per-protocol analyses and consistent across subgroups, sensitivity analyses and by individual GLP-1 RA agent. Mortality analyses were limited by small sample sizes but suggested a potential survival benefit.</p><p><strong>Conclusions: </strong>GLP-1 RA initiation was associated with lower HCC risk versus several comparators. Mortality findings were inconclusive and exploratory, warranting confirmation in larger studies.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722272","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":"Hepatic fibrosis severity assessed by FIB-4 index is independently associated with reduced kidney function in patients with metabolic dysfunction-associated steatotic liver disease: a nationwide multicenter study from Türkiye.","authors":"Hilmi Erdem Sumbul, Ali Kirik, Selcuk Yaylaci, Alihan Oral, Sibel Ocak Serin, Kubilay Issever, Nizameddin Koca, Ahmet Aydin, Ismail Demir, Nevzat Gozel, Pinar Yildiz, Oguzhan Sitki Dizdar, Enes Seyda Sahiner, Seyit Uyar, Emin Gemcioglu, Hasan Esat Yucel, Cem Sahin, Hasan Sozel, Osman Ozudogru, Gokhan Tazegul, Melisa Sahin Tekin, Emel Saglam, Begum Seyda Avci, Erdinc Gulumsek, Huseyin Ali Ozturk, Demet Yalcin Kehribar, Hasan Tunca, Elif Duygu Topan, Tuba Taslamacioglu Duman, Abdullah Tanrikulu, Hakan Sivgin, Hikmet Oztop, Muhammet Ozbilen, Necip Nas, Mehmet Selim Mamis, Ozge Kurtkulagi, Kamil Konur, Ismail Kirli, Fatih Kamis, Ozge Kama Basci, Ahmed Bilal Genc, Muzeyyen Eryilmaz, Betül Erismis, Yasin Sahinturk, Nur Duzen Oflas, Erkan Dulkadiroglu, Ayse Kevser Demir, Deniz Cekic, Erkan Cakmak, Hatice Beyazal Polat, Hilal Bektas Uysal, Turkan Pasali Kilit, Sibel Demiral Sezer, Emine Binnetoglu, Esref Arac, Ihsan Solmaz, Hacer Sen, Gulali Aktas, Burcin Meryem Atak Tel, Lale Saka Baraz, Bahri Abayli, Hale Akan, Canan Akkus, Berrin Aksakal, Sami Bahcebasi, Orhan Balikci, Muharrem Bayrak, Omer Faruk Alakus, Ifakat Irem Bicer, Rifat Bozkus, Bilgin Bahadir Basgoz, Fatih Coskun, Cuneyt Cagatay, Feride Caglar, Ulfet Deger, Ali Erol, Aysegul Ertinmaz, Melis Gokgoz, Fatih Ileri, Ugur Can Izlimek, Aynur Kamburoglu, Sanem Kayhan, Yusuf Kimyon, Seref Enes Kocaman, Celalettin Kucuk, Hatice Metin, Oktay Olmuscelik, Erkan Ozdemir, Ensar Ozmen, Hatice Ozge Serin, Ahmet Veli Sanibas, Ece Unal Cetin, Nazif Yalcin, Mehmet Serdar Yildirim, Hasan Esat Yildirim, Huseyin Yildiz, Oguzhan Zengin, Ali Zeynettin, Fatih Atik, Selin Muge Aslan, Nurcan Aslan, Sare Babacan Celikel, Suat Baran Bakan, Bektas Isik, Cisem Yilmaz, Ahmet Gazi Mustan, Cahit Dincer, Yagmur Sena Tosun, Rabia Ulutas, Tugce Nur Yazici, Emrah Yilmaz, Muhammed Rasit Altinisik, Bercem Berent, Hamit Yildiz, Ramazan Azim Okyay","doi":"10.1007/s12072-026-11139-8","DOIUrl":"10.1007/s12072-026-11139-8","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with extrahepatic organ damage, including chronic kidney disease (CKD). The Fibrosis-4 (FIB-4) index is a validated non-invasive tool for estimating hepatic fibrosis severity. This study aimed to investigate whether FIB-4-defined hepatic fibrosis is independently associated with reduced estimated glomerular filtration rate (eGFR) in a large, real-world Turkish MASLD cohort.</p><p><strong>Methods: </strong>This is a cross-sectional analysis of the prospective, nationwide, multicenter DAHUDER MASLD Study, which enrolled patients from 44 internal medicine outpatient clinics across 31 provinces representing all 12 statistical regions of Türkiye. A total of 10,873 MASLD patients were included. MASLD was defined as ultrasonographic hepatic steatosis in the presence of at least one cardiometabolic risk factor. High FIB-4 was defined as ≥ 1.3 for patients aged < 65 years and ≥ 2.0 for those aged ≥ 65 years, per EASL-EASD-EASO 2024 guidelines. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Age-stratified multivariate linear regression models were constructed to identify independent predictors of eGFR.</p><p><strong>Results: </strong>High FIB-4 was detected in 11.2% of the patients (n = 1219). Patients with high FIB-4 had significantly lower eGFR compared to those with low FIB-4 (85.37 ± 21.08 vs. 94.18 ± 20.17 mL/min/1.73 m², p < 0.001). FIB-4 score was negatively correlated with eGFR (r =  - 0.149, p < 0.001). In age-stratified multivariate analysis adjusted for diabetes mellitus, hypertension, BMI, sex, SGLT2 inhibitor use, and uric acid, FIB-4 score remained an independent predictor of reduced eGFR in both age groups (< 65 years: B =  - 2.586, 95% CI [- 3.025, - 2.148], p < 0.001; ≥ 65 years: B =  - 1.384, 95% CI [- 2.326, - 0.443], p = 0.004). eGFR decreased progressively across cardiometabolic risk score categories, from approximately 105 mL/min/1.73 m² (score 1) to approximately 87 mL/min/1.73 m² (score 5). KDIGO-based staging revealed a higher prevalence of advanced CKD stages in the high FIB-4 group (p < 0.001).</p><p><strong>Conclusions: </strong>Hepatic fibrosis severity, as quantified by the FIB-4 index, is independently associated with impaired kidney function in patients with MASLD beyond established cardiometabolic risk factors. These findings support the role of FIB-4 as a simple, cost-effective tool for integrated cardio-hepato-renal risk stratification. Clinicians should systematically monitor renal function in MASLD patients, particularly those with elevated FIB-4 scores.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721519","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":"National guideline for hepatitis B elimination in Thailand: a decentralized health system model for expanding diagnosis and treatment.","authors":"Phunchai Charatcharoenwitthaya, Tawesak Tanwandee, Pisit Tangkijvanich, Teerha Piratvisuth, Chatree Jullapetch, Cheewanan Lertpiriyasuwat, Pongtorn Chartpitak","doi":"10.1007/s12072-026-11135-y","DOIUrl":"https://doi.org/10.1007/s12072-026-11135-y","url":null,"abstract":"<p><p>Despite sustained universal infant hepatitis B vaccination, chronic hepatitis B (CHB) remains an important cause of cirrhosis and hepatocellular carcinoma in Thailand, particularly among adults born before vaccine implementation. This article summarizes the 2026 National Guideline on Elimination of Viral Hepatitis B in Thailand and presents a health-system framework for addressing the remaining disease burden. The guideline was developed by a multidisciplinary expert panel using evidence from international recommendations, peer-reviewed literature, national epidemiological data, implementation studies, and health economic analyses. The recommendations were formulated using the GRADE framework and adapted for implementation within Thailand's Universal Health Coverage system. The national strategy prioritizes birth-cohort HBsAg screening for adults born before 1992, simplified evidence-based treatment eligibility incorporating non-invasive fibrosis assessment and virological criteria, and first-line use of high genetic-barrier nucleos(t)ide analogs. Prevention of mother-to-child transmission prioritizes HBV DNA-guided antiviral prophylaxis, with simplified implementation pathways reserved for settings with substantial diagnostic constraints. Long-term care emphasizes structured monitoring, appropriate specialist referral, conservative treatment discontinuation criteria, defined retreatment thresholds, and risk-based semiannual ultrasound surveillance for hepatocellular carcinoma. Integration with antenatal services, HIV programs, and primary care facilities supports decentralized delivery and continuity of care. Thailand's 2026 hepatitis B guideline operationalizes evidence-based CHB management within a publicly financed decentralized health system and provides a scalable model for expanding hepatitis B diagnosis and treatment in endemic settings.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669420","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 letter to the editor \"Diagnostic criteria for fatty liver disease: lessons from other diseases\".","authors":"Yun Kyung Cho, Chang Hee Jung","doi":"10.1007/s12072-026-11047-x","DOIUrl":"10.1007/s12072-026-11047-x","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1262-1263"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124805","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":"Letter regarding the ANCHOR trial: methodological perspectives on GM-CSF efficacy and HBsAg prediction.","authors":"Xiaolong Lu, Meng Li, Ximeng Ren, Yao Song, Shuangshuang Liu, Yang Liu","doi":"10.1007/s12072-025-11032-w","DOIUrl":"10.1007/s12072-025-11032-w","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1255-1256"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348256","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":"Clinical clustering identifies MASLD subtypes with distinct longitudinal cardiovascular risks and lipidomic profiles.","authors":"Zhixin Tu, Yu Ding, Tong Yue, Hongqiang Zhang, Ting Peng, Pingting Yang, Weiwei Qin, Jiangang Wang, Jianping Weng, Sihui Luo","doi":"10.1007/s12072-026-11103-6","DOIUrl":"10.1007/s12072-026-11103-6","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits substantial heterogeneity in progression and cardiovascular outcomes. We aimed to identify reproducible MASLD subtypes in Chinese cohorts, characterize their distinct lipidomic profiles, and evaluate their associations with long-term cardiovascular outcomes.</p><p><strong>Methods: </strong>We investigated the heterogeneity of MASLD using k-means clustering based on six simple clinical variables in a cohort of 5,329 individuals. The identified clusters were applied in an independent cohort of 1,432 participants. Cardiovascular outcomes were compared across clusters using Kaplan-Meier curves and log-rank tests. Untargeted lipidomic profiling was performed with partial least squares discriminant analysis and least absolute shrinkage and selection operator regression to identify discriminative lipids for XGBoost model. Feature importance was evaluated using SHapley Additive exPlanations.</p><p><strong>Results: </strong>Three distinct MASLD subtypes were identified. Cluster A (Metabolic-Obesity subtype), characterized by the highest BMI and triglycerides with the lowest risk of cardiovascular outcomes. Cluster B (Dysglycemic subtype) distinguished by increased glycated hemoglobin. Cluster C (Aging-Hypertensive subtype) was primarily associated with age, blood pressure, and fibrosis markers, leading to higher risk of cardiovascular outcomes. Lipidomics identified 1061 metabolites, and ten lipids distinguishing the Cluster A and C were selected for modeling, yielding an area under the receiver operating characteristic curve of 0.900. Pathway enrichment analysis further revealed the Cluster C involved in sphingolipid metabolism.</p><p><strong>Conclusions: </strong>Three distinct MASLD subtypes with varying metabolic features and cardiovascular risks were identified in Chinese cohorts. The Aging-Hypertensive subtype showed the highest cardiovascular risk and was associated with dysregulated sphingolipid metabolism. These findings underscore the clinical heterogeneity of MASLD and highlight the need for risk classification and personalized intervention strategies.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1047-1057"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029667","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":"APASL_2026_Istanbul.","authors":"","doi":"10.1007/s12072-026-11095-3","DOIUrl":"10.1007/s12072-026-11095-3","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1-806"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701208","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":"Spatial analysis identifies LAMTOR2 overexpression in hepatocellular carcinoma with vessels encapsulating tumor clusters.","authors":"Yoon Jung Hwang, San Ha Hwang, Min Ji Kang, Geon Woo Park, Hyeewon Seo, Hyejung Lee, Hyun Je Kim, Suk Kyun Hong, Haeryoung Kim","doi":"10.1007/s12072-026-11115-2","DOIUrl":"10.1007/s12072-026-11115-2","url":null,"abstract":"<p><strong>Background: </strong>Vessels encapsulating tumor clusters (VETC) is a distinct angiogenic pattern in hepatocellular carcinoma (HCC). While VETC-positive HCC is associated with poor prognosis, it demonstrates improved responses to vascular-targeted therapies. However, the molecular signatures that define VETC-positive HCC remain elusive. This study employed spatial transcriptomics and single-cell RNA sequencing to characterize the molecular landscape of VETC-positive HCC and identify candidate biomarkers.</p><p><strong>Methods: </strong>Using GeoMx Digital Spatial Profiling, we analyzed tumor and adjacent liver tissues from 24 HCC patients, focusing on VETC-positive, VETC-negative, or non-neoplastic liver regions. Differential gene expression and pathway enrichment analyses were performed. Candidate genes were further evaluated using immunohistochemistry, The Cancer Genome Atlas (TCGA) dataset, and single-cell RNA sequencing.</p><p><strong>Results: </strong>Spatial transcriptomic analysis identified 39 genes upregulated in VETC-positive regions, with enrichment of angiogenesis, WNT/β-catenin, Hedgehog, and p53 signaling, epithelial-mesenchymal transition, and fatty acid metabolism pathways, and suppression of immune-related pathways. Among these, LAMTOR2, DPP4, ZNHIT1, and MLXIPL were consistently upregulated in VETC-positive regions compared to both VETC-negative and normal liver regions. LAMTOR2 demonstrated tumor-specific localization in TCGA dataset. Immunohistochemistry confirmed that peripheral accentuation pattern of LAMTOR2 expression was restricted to tumor cells and strongly correlated with RNA expression and VETC positivity. Single-cell RNA sequencing further revealed LAMTOR2 upregulation in malignant hepatocytes, particularly within VETC-high subpopulations enriched for lipid degradation, fatty acid oxidation, and detoxification pathways.</p><p><strong>Conclusion: </strong>VETC-positive HCC exhibits a distinct transcriptomic and metabolic profile. LAMTOR2, which is consistently upregulated in VETC-positive HCCs, may contribute to angiogenic and metabolic reprogramming, offering potential implications for therapeutic stratification in HCC.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1150-1161"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148328788","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":"Refining the assessment of cardiac dysfunction in MAFLD and MASLD: a commentary on study limitations.","authors":"Zhuo Liu, Zhihui Xu, Nan Wang","doi":"10.1007/s12072-025-10990-5","DOIUrl":"10.1007/s12072-025-10990-5","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1227-1228"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700717","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":"Methodological considerations for interpreting associations between fatty liver disease definitions and cardiac diastolic function.","authors":"Hui-Chin Chang, Shuo-Yan Gau","doi":"10.1007/s12072-025-10982-5","DOIUrl":"10.1007/s12072-025-10982-5","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":"1233-1234"},"PeriodicalIF":7.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668209","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}