Hepatology最新文献

{"title":"Weight reduction-dependent/-independent effects of survodutide on liver endpoints: Mediation analysis of a phase 2 trial in MASH.","authors":"Mazen Noureddin, Arun J Sanyal, Pierre Bedossa, Mandy Fraessdorf, Corinna Schoelch, Elena Startseva, S Renée Marshall, Ahmad Alhussein, Guy W Neff, Eric J Lawitz, Elisabetta Bugianesi, Quentin M Anstee, Philip N Newsome, Vlad Ratziu, Azadeh Hosseini-Tabatabaei, Jörn M Schattenberg, Naim Alkhouri, Ramy Younes","doi":"10.1097/HEP.0000000000001825","DOIUrl":"10.1097/HEP.0000000000001825","url":null,"abstract":"<p><strong>Background and aims: </strong>Survodutide was associated with improvements in liver-related endpoints in a phase 2 trial in MASH (NCT04771273). This post hoc mediation analysis evaluated the proportion of the direct treatment effect versus the indirect effect mediated by weight reduction.</p><p><strong>Approach and results: </strong>Data were included for participants with fibrosis stages F2-F3 and paired baseline/end-of-treatment biopsy readings; survodutide dose arms were pooled. The causal mediation analysis model included treatment (exposure) and percentage change in body weight (mediator), with baseline body weight, type 2 diabetes status, and fibrosis stage as covariates. Outcomes included histological endpoints and non-invasive tests (NITs) after 48 weeks' treatment. Total, direct (weight reduction-independent), and indirect (weight reduction-dependent) treatment effects were calculated for survodutide versus placebo. This analysis included 170 participants. For histological endpoints, the percentage of the total treatment effect mediated by weight reduction (indirect effect) was estimated at 66.7% for resolution of MASH without worsening of fibrosis, 71.8% for improvement in MASH without worsening of fibrosis, and 36.3% for improvement in fibrosis without worsening of MASH (suggesting a greater direct effect). Similarly, for NITs related to inflammation/fibrosis, <50% of the total effect was mediated by weight reduction [16.5% (AST)-38.6% (Enhanced Liver Fibrosis)]. For steatosis-related endpoints (MRI-proton density fat fraction and FibroScan Controlled Attenuation Parameter), a higher proportion was mediated by weight reduction (58.2% and 77.4%, respectively).</p><p><strong>Conclusions: </strong>Endpoints related to improvements in inflammation/fibrosis were predominantly weight reduction-independent, suggestive of a potential role of direct glucagon receptor agonism in the liver.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-assisted tumor radiomic dynamics on MRI predict pathological complete response in HCC undergoing immune-based therapy followed by hepatectomy.","authors":"Shi-Qi Zhou, Lu-Na Wang, Li-Fang Wu, Li-Yu Sun, Yu-Chen Yang, Zi-Yue Yang, Zi-Yi Wang, Tian He, Fei Li, Ling-Li Chen, Hui Li, Xiao-Dong Zhu, Ying-Hao Shen, Cheng Huang, Yuan Ji, Qiang Gao, Jian Zhou, Jia Fan, Yong-Jun Chen, Tian-Qiang Song, Bin Xu, Hui-Chuan Sun","doi":"10.1097/HEP.0000000000001724","DOIUrl":"10.1097/HEP.0000000000001724","url":null,"abstract":"<p><strong>Background and aims: </strong>Pathological complete response (pCR) following conversion therapy for initially unresectable hepatocellular carcinoma (uHCC) remains challenging to predict preoperatively. This study developed and validated a model integrating clinicopathological and radiomic features of the tumor to predict pCR.</p><p><strong>Methods: </strong>In this multicenter retrospective study, temporal radiomics features were extracted from baseline, post-treatment, and delta (change) MRIs. Serum AFP response was calculated as log₁₀(preoperative AFP)/log₁₀(baseline AFP). Univariate analysis, collinearity assessment, LASSO, and random forest were employed to perform feature selection. Fourteen machine learning models were benchmarked, with performance evaluated by using comprehensive metrics AUC, NPV, PPV, sensitivity, specificity, calibration, and decision curve analysis.</p><p><strong>Results: </strong>The model was developed and validated in a training (n=78), an internal test (n=32), and an independent validation cohort (n=44). The delta radiomic model significantly outperformed both baseline (test AUC: 0.835 vs. 0.483, p <0.05; validation AUC: 0.783 vs. 0.434, p <0.05) and preoperative models (test AUC: 0.685, p <0.05; validation AUC: 0.506, p <0.05), demonstrating superior predictive performance and generalization capability in predicting lesion-level pCR. Notably, when predicting patient-level pCR, the radiomic model also showed robust discrimination, with AUCs of 0.819 in the test set and 0.781 in the validation set. The combined radiomics-AFP model achieved even higher AUCs of 0.920 (test) and 0.857 (validation) in predicting lesion-level pCR.</p><p><strong>Conclusions: </strong>Dynamic radiomic changes effectively predict pCR in uHCC after conversion therapy. Combining delta radiomics with AFP response significantly improves predictive performance, offering a non-invasive method for assessing pCR and potentially guiding personalized treatment decisions.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"453-468"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Survival analysis pitfalls in MASLD: Proportional hazards, immortal time, and follow-up discrepancies.","authors":"Jian Huang","doi":"10.1097/HEP.0000000000001615","DOIUrl":"10.1097/HEP.0000000000001615","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E34-E35"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145706706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Survival analysis pitfalls in MASLD-Proportional hazards, immortal time, and follow-up discrepancies.","authors":"Yu Shi, Ruoqi Zhou, Yuanjie Pang, Vincent Wai-Sun Wong, Ming-Hua Zheng","doi":"10.1097/HEP.0000000000001618","DOIUrl":"10.1097/HEP.0000000000001618","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E36-E37"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistent efficacy of efruxifermin across PNPLA3 genotypes in phase 2b trials in MASH.","authors":"Naga Chalasani, Erik J Tillman, Sonja K Billes, Timothy Rolph, Mazen Noureddin","doi":"10.1097/HEP.0000000000001792","DOIUrl":"10.1097/HEP.0000000000001792","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"617-620"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Reciprocal regulation between forkhead box M1/NF-κB and methionine adenosyltransferase 1A drives liver cancer.","authors":"Yuan Li, Liqing Lu, Jian Tu, Jing Zhang, Ting Xiong, Wei Fan, Jiaohong Wang, Meng Li, Yibu Chen, Justin Steggerda, Hui Peng, Yongheng Chen, Tony Wh Li, Zhi-Gang Zhou, José M Mato, Ekihiro Seki, Ting Liu, Heping Yang, Shelly C Lu","doi":"10.1097/HEP.0000000000001777","DOIUrl":"10.1097/HEP.0000000000001777","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E46-E47"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148160960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multisociety consensus statement on a new common definition and diagnostic criteria for PSVD or NCPF.","authors":"Virginia Hernandez-Gea, Valerie Paradis, Maha Guindi, Venancio A F Alves, Amal Aqul, Eira Cerda, Sarwa Darwish Murad, Prasenjit Das, Angelo Di Giorgio, Luiz A R de Freitas, Tassos Grammatikopoulos, Kenichi Harada, Nelia Hernandez, Samar H Ibrahim, Sanjay Kakar, Saul Karpen, David E Kleiner, Necati Ormeci, Xiaolong Qi, Puja Sakhuja, Maria Isabel Schinoni, Romil Saxena, Alexandre Sayadi, Akash Shukla, Dina G Tiniakos, Elizabeth Verna, Kerry Wong, Laure Elkrief, Christine Sempoux, Theo Heller, Pierre-Emmanuel Rautou","doi":"10.1097/HEP.0000000000001768","DOIUrl":"10.1097/HEP.0000000000001768","url":null,"abstract":"<p><p>Noncirrhotic portal hypertension has historically been described using heterogeneous and region-specific terminology-such as idiopathic portal hypertension (IPH), noncirrhotic portal fibrosis (NCPF), obliterative portal venopathy, and nodular regenerative hyperplasia-leading to substantial variability in diagnosis, reporting, and international research collaboration. Differences in guideline definitions from major societies (AASLD, EASL, and APASL), together with the presence of characteristic histologic lesions in patients without clinically overt portal hypertension, have further complicated disease classification. To address these challenges, a large, multisociety, international initiative was convened to harmonize nomenclature and diagnostic criteria. Representatives from liver, pathology, and pediatric hepatology societies across the Americas, Europe, and Asia participated in a structured consensus process that included specialized working groups and external Delphi validation. The initiative produced a globally harmonized and implementable diagnostic framework. Consensus was reached that the terms porto-sinusoidal vascular disorder (PSVD) and NCPF may be used interchangeably when identical diagnostic criteria are applied, and that they should be written as PSVD or NCPF . The diagnosis was defined as fundamentally clinicopathological, requiring integrated assessment. Core principles include the need for a high-quality liver biopsy (≥10 mm), mandatory exclusion of cirrhosis, and systematic exclusion of specific alternative conditions. Importantly, the consensus recognizes that PSVD or NCPF may be diagnosed even without clinical portal hypertension and may coexist with other liver diseases, provided cirrhosis is excluded. Standardized major and minor histologic criteria were developed collaboratively by expert pathologists and externally validated. Features of portal hypertension were harmonized into specific and nonspecific categories applicable to routine clinical practice. An integrated diagnostic scoring system incorporating histology, clinical features, associated conditions, and concommitant etiologies was developed and validated using the Delphi method. This consensus provides the first internationally endorsed, unified framework for the diagnosis of PSVD or NCPF. Its global implementation is expected to reduce diagnostic variability, improve comparability across regions, and facilitate the development of robust, internationally harmonized clinical and translational research cohorts.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"601-616"},"PeriodicalIF":18.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of new obesity definitions in the classification and outcomes of patients with MASLD.","authors":"Jie Cai, Terry Cheuk-Fung Yip, Huapeng Lin, Grace Lai-Hung Wong, Andrea On-Yan Luk, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jérôme Boursier, José Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Arun J Sanyal, Victor de Lédinghen, Philip N Newsome, Jian-Gao Fan, Laurent Castéra, Manuel Romero-Gomez, Alice Pik-Shan Kong, Seung Up Kim, Jian Sun, Vincent Wai-Sun Wong","doi":"10.1097/HEP.0000000000001827","DOIUrl":"10.1097/HEP.0000000000001827","url":null,"abstract":"<p><strong>Background and aims: </strong>New obesity definitions beyond body mass index (BMI) have recently been proposed. This study aimed to assess the proportion of obesity under these frameworks and their associations with liver-related events (LREs).</p><p><strong>Approach and results: </strong>We analyzed data from the multinational vibration-controlled transient elastography (VCTE)-prognosis cohort of 12,583 patients with metabolic dysfunction-associated steatotic liver disease. Obesity was defined using 3 frameworks: BMI alone, the European Association for the Study of Obesity (EASO) criteria (BMI-defined obesity or overweight with waist-to-height ratio ≥0.5 plus comorbidity), and the Lancet Commission criteria (BMI-defined obesity plus ≥1 elevated anthropometric measure, or ≥2 elevated anthropometric measures, or BMI ≥40 kg/m²). LRE incidence per 1000 person-years was 2.4 (95% CI: 1.5-3.7), 3.4 (95% CI: 2.6-4.5), and 5.2 (95% CI: 4.3-6.3) for BMI-defined normal weight, overweight, and obesity. Overall, 20.4% and 34.1% of patients were not classified as obese by BMI but met obesity criteria under the EASO and Lancet definitions. These newly classified obese groups did not have higher LRE risk compared with their nonobese counterparts (adjusted subdistribution HR 1.15 [0.64-2.08] for EASO; 0.75 [0.42-1.34] for Lancet ), with incidence rates of 2.9 (95% CI: 1.9-4.3) and 2.7 (95% CI: 1.8-3.9) per 1000 person-years. LRE risk increased significantly only when the waist-to-height ratio approached 0.6.</p><p><strong>Conclusions: </strong>New obesity definitions broadened the obesity population but did not improve LRE prediction over BMI alone. Higher waist-based thresholds warrant further evaluation.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: RNF128 aggravates metabolic dysfunction-associated steatotic liver disease progression via stabilization of SCD1.","authors":"Lei Cao, Wei Yang, Chaofan Wang, Changhao Liu, Wenqian Qi, Ruiqing Ren, Jie Zhang, Shuting Yu, Qian Li, Liangyu Cai, Xinyu Zhang, Xiaohong Wang, Wenhai Sui, Meng Zhang, Cheng Zhang","doi":"10.1097/HEP.0000000000001817","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001817","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The weight of progress: Why dynamic weight trajectories matter in MASLD","authors":"Guneet Sidhu","doi":"10.1097/hep.0000000000001800","DOIUrl":"https://doi.org/10.1097/hep.0000000000001800","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"154 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}