Background: Tirzepatide (TZP) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have both shown promise in managing metabolic dysfunction-associated steatotic liver disease (MASLD). However, direct comparative data are limited. This study aimed to evaluate the real-world effectiveness of TZP versus SGLT2i in adults with MASLD.
Methods: We conducted a retrospective, multi-institutional cohort study using the TriNetX global research network. Adults (≥ 18 years) with a diagnosis of MASLD who were newly initiated on TZP or SGLT2i between January 1, 2022, and June 30, 2025, were included. The primary outcome was a composite of all-cause mortality, major adverse cardiovascular events (MACEs), and major adverse liver outcomes (MALOs). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: After 1:1 propensity score matching, 23,106 patients were included in each group. Compared to SGLT2i, TZP use was associated with a significantly lower risk of the primary composite outcome (HR, 0.72; 95% CI, 0.63-0.83). TZP was also associated with lower risks of all-cause mortality (HR, 0.55; 95% CI, 0.43-0.71), MACEs (HR, 0.68; 95% CI, 0.58-0.80), and MALOs (HR, 0.66; 95% CI, 0.54-0.80). These associations were consistent across subgroups stratified by age, sex, BMI, and comorbidities.
Conclusions: In this large real-world study, TZP was associated with significantly better clinical outcomes than SGLT2i in adults with MASLD. These findings support TZP as a preferred treatment option and highlight the need for prospective trials to validate these results.
{"title":"Tirzepatide versus SGLT2 inhibitors for MASLD: a multi-institutional propensity score-matched cohort study.","authors":"Jheng-Yan Wu, Yu-Min Lin, Wan-Hsuan Hsu, Ting-Hui Liu, Ya-Wen Tsai, Po-Yu Huang, Min-Hsiang Chuang, Tsung Yu, Chih-Cheng Lai","doi":"10.1007/s12072-025-11021-z","DOIUrl":"https://doi.org/10.1007/s12072-025-11021-z","url":null,"abstract":"<p><strong>Background: </strong>Tirzepatide (TZP) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have both shown promise in managing metabolic dysfunction-associated steatotic liver disease (MASLD). However, direct comparative data are limited. This study aimed to evaluate the real-world effectiveness of TZP versus SGLT2i in adults with MASLD.</p><p><strong>Methods: </strong>We conducted a retrospective, multi-institutional cohort study using the TriNetX global research network. Adults (≥ 18 years) with a diagnosis of MASLD who were newly initiated on TZP or SGLT2i between January 1, 2022, and June 30, 2025, were included. The primary outcome was a composite of all-cause mortality, major adverse cardiovascular events (MACEs), and major adverse liver outcomes (MALOs). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>After 1:1 propensity score matching, 23,106 patients were included in each group. Compared to SGLT2i, TZP use was associated with a significantly lower risk of the primary composite outcome (HR, 0.72; 95% CI, 0.63-0.83). TZP was also associated with lower risks of all-cause mortality (HR, 0.55; 95% CI, 0.43-0.71), MACEs (HR, 0.68; 95% CI, 0.58-0.80), and MALOs (HR, 0.66; 95% CI, 0.54-0.80). These associations were consistent across subgroups stratified by age, sex, BMI, and comorbidities.</p><p><strong>Conclusions: </strong>In this large real-world study, TZP was associated with significantly better clinical outcomes than SGLT2i in adults with MASLD. These findings support TZP as a preferred treatment option and highlight the need for prospective trials to validate these results.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970712","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}
Pub Date : 2026-01-13DOI: 10.1007/s12072-025-11014-y
Yongjie Zhou, Jingqin Ma, Yaozu Liu, Li Ma, Jiaze Yu, Minjie Yang, Zhiping Yan, Wen Zhang, Jianjun Luo
{"title":"Correction: Comparison of the impact of shunting the left versus right portal vein branch during TIPS on the postoperative overt hepatic encephalopathy: a randomized trial.","authors":"Yongjie Zhou, Jingqin Ma, Yaozu Liu, Li Ma, Jiaze Yu, Minjie Yang, Zhiping Yan, Wen Zhang, Jianjun Luo","doi":"10.1007/s12072-025-11014-y","DOIUrl":"10.1007/s12072-025-11014-y","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958950","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}
Pub Date : 2026-01-06DOI: 10.1007/s12072-025-11011-1
Tamoghna Biswas, Bikrant Bihari Lal, Seema Alam
{"title":"Author's response to the letter to editor: \"Comment on 'Cirrhotic cardiomyopathy in children with biliary atresia and genetic intrahepatic cholestasis: clinical course and outcomes\".","authors":"Tamoghna Biswas, Bikrant Bihari Lal, Seema Alam","doi":"10.1007/s12072-025-11011-1","DOIUrl":"https://doi.org/10.1007/s12072-025-11011-1","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911306","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}
Pub Date : 2026-01-04DOI: 10.1007/s12072-025-10999-w
Yi Shen, Dan Zhou, Jie Sun, Xiaoze Wang, Ruoting Men, Maoyao Wen, Xiaoli Fan, Xianglin Wang, Fan Yang, Li Yang
Background and aim: Heterogeneous diagnostic criteria for acute autoimmune hepatitis (AIH) across studies hinder the characterization of genuine acute AIH. We developed stringent and multidimensional criteria to distinguish acute, acute-on-chronic, and chronic autoimmune hepatitis (A-AIH, AC-AIH, and C-AIH), aiming to elucidate their clinical profiles.
Methods: We consecutively enrolled patients diagnosed with definite AIH between 2012 and 2024. All patients were stratified using stringent criteria encompassing onset time (A-AIH: < 6 months), acute presentation (total bilirubin (TB) ≥ 5 mg/dL or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 10 × upper limits of normal (ULN)), imaging evidence of cirrhosis, and histological fibrosis stage (A-AIH: fibrosis stage ≤ 1). Clinical features and treatment responses were compared across the three groups.
Results: Among 235 patients, 10.6% were classified as A-AIH, 57.9% as AC-AIH, and 31.5% as C-AIH, with a median follow-up of 51.9 (IQR 21.8-78.8) months. The cumulative full biochemical remission (FBR) rate was 92.0% in A-AIH, 75.7% in AC-AIH, and 59.5% in C-AIH (p = 0.003). The median FBR times were 2.9, 5.5, and 14.5 months, respectively (p = 0.002). Liver-related mortality rates were 0%, 8.8%, and 16.2% across the three groups (p = 0.021). Cirrhosis and albumin (ALB) levels were independent predictors of FBR, and ALB was also independently associated with liver-related death.
Conclusion: Patients with A-AIH achieved the highest cumulative FBR rate, whereas those with C-AIH had the poorest treatment response and the highest liver-related mortality.
{"title":"Genuine acute autoimmune hepatitis has better therapeutic response and prognosis.","authors":"Yi Shen, Dan Zhou, Jie Sun, Xiaoze Wang, Ruoting Men, Maoyao Wen, Xiaoli Fan, Xianglin Wang, Fan Yang, Li Yang","doi":"10.1007/s12072-025-10999-w","DOIUrl":"https://doi.org/10.1007/s12072-025-10999-w","url":null,"abstract":"<p><strong>Background and aim: </strong>Heterogeneous diagnostic criteria for acute autoimmune hepatitis (AIH) across studies hinder the characterization of genuine acute AIH. We developed stringent and multidimensional criteria to distinguish acute, acute-on-chronic, and chronic autoimmune hepatitis (A-AIH, AC-AIH, and C-AIH), aiming to elucidate their clinical profiles.</p><p><strong>Methods: </strong>We consecutively enrolled patients diagnosed with definite AIH between 2012 and 2024. All patients were stratified using stringent criteria encompassing onset time (A-AIH: < 6 months), acute presentation (total bilirubin (TB) ≥ 5 mg/dL or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 10 × upper limits of normal (ULN)), imaging evidence of cirrhosis, and histological fibrosis stage (A-AIH: fibrosis stage ≤ 1). Clinical features and treatment responses were compared across the three groups.</p><p><strong>Results: </strong>Among 235 patients, 10.6% were classified as A-AIH, 57.9% as AC-AIH, and 31.5% as C-AIH, with a median follow-up of 51.9 (IQR 21.8-78.8) months. The cumulative full biochemical remission (FBR) rate was 92.0% in A-AIH, 75.7% in AC-AIH, and 59.5% in C-AIH (p = 0.003). The median FBR times were 2.9, 5.5, and 14.5 months, respectively (p = 0.002). Liver-related mortality rates were 0%, 8.8%, and 16.2% across the three groups (p = 0.021). Cirrhosis and albumin (ALB) levels were independent predictors of FBR, and ALB was also independently associated with liver-related death.</p><p><strong>Conclusion: </strong>Patients with A-AIH achieved the highest cumulative FBR rate, whereas those with C-AIH had the poorest treatment response and the highest liver-related mortality.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896425","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}
Pub Date : 2026-01-03DOI: 10.1007/s12072-025-10970-9
Huikang Wang, Xinjun Xu, Xicheng Song, Yu Zhang
{"title":"Comment on \"Efficacy and safety of atezolizumab and bevacizumab with or without TACE as first-line therapy for unresectable HCC: a multicenter cohort study\".","authors":"Huikang Wang, Xinjun Xu, Xicheng Song, Yu Zhang","doi":"10.1007/s12072-025-10970-9","DOIUrl":"https://doi.org/10.1007/s12072-025-10970-9","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892322","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}
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