Background/Aims Information about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.
Methods Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).
Result s: In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39–0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86–0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86–0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64–0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77–0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60–0.77.
Conclusions In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.
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Tirzepatide versus SGLT2 inhibitors for MASLD: a multi-institutional propensity score-matched cohort study 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 Hepatology International.2026;[Epub] CrossRef
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NHANES Xingyu Yao, Kaiwen Xiao, Hein Ko Oo Hormone and Metabolic Research.2025; 57(09): 511. CrossRef
Background/Aims With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the USA. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.
Methods Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related and non-liver-related mortality were analyzed.
Result s: Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; p<0.0001), liver-related (3.3% vs. 14%; p<0.0001), and non-liver-related mortality (22.3% vs. 26.9%; p=0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR]=0.63; p<0.0001), liver-related (aHR=0.24; p<0.0001), and non-liverrelated (aHR=0.81; p=0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR=0.39; p<0.0001) whereas open surgeries were associated with higher overall mortality (aHR=1.24; p=0.022).
Conclusions Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.
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Differential Characteristics and Survival Outcomes of Patients With Cirrhosis According to Underlying Liver Aetiology Yu Shi, Nicholas Chien, Ashley Fong, Vy H. Nguyen, Surya Teja Gudapati, Angela Chau, Sally Tran, Linda Henry, Ramsey Cheung, Changqing Zhao, Minjuan Jin, Mindie H. Nguyen Alimentary Pharmacology & Therapeutics.2025; 61(10): 1622. CrossRef
A leap in the dark: Bariatric surgery for treatment of metabolic dysfunction-associated steatotic liver disease related cirrhosis: Editorial on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic live Jing Zeng, Jian-Gao Fan Clinical and Molecular Hepatology.2025; 31(2): 610. CrossRef
Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis” Wei Wang, Yating Xie, Ailei Xu Clinical and Molecular Hepatology.2025; 31(2): e143. CrossRef
Advancing precision medicine in metabolic dysfunction-associated steatotic liver disease Bryan A. Priego-Parra, Rocío Gallego-Durán, Berenice M. Román-Calleja, José Antonio Velarde-Ruiz Velasco, Manuel Romero-Gómez, Jordi Gracia-Sancho Trends in Endocrinology & Metabolism.2025; 36(11): 1000. CrossRef
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Reply to correspondence on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis” Jing Zeng, Jian-Gao Fan Clinical and Molecular Hepatology.2025; 31(2): e218. CrossRef
Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis” Weixiong Zhu, Xuefan Zeng, Zengxi Yang, Yusheng Cheng, Wence Zhou Clinical and Molecular Hepatology.2025; 31(3): e252. CrossRef
Association between body roundness index and risks of all-cause and cardiovascular mortality in adults with metabolic dysfunction-associated steatotic liver disease: NHANES 1999–2018 Yanshan Yi, Li Yang Frontiers in Nutrition.2025;[Epub] CrossRef
Letter to the editor on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis” Chi-Kuei Hsu, Po-Yu Huang, Chih-Cheng Lai Clinical and Molecular Hepatology.2025; 31(3): e247. CrossRef
Efficacy and Safety of Bariatric Surgery in Well-Compensated Liver Cirrhosis: A Systematic Review and a Single-Arm Meta-analysis Pandora Fonseca, Leonardo Pereira, João Gabriel Braga, Giovanna Macanhã Scremin, Luísa de Araujo, Julia Alves, Gabriel de França, Pedro Bregion, Rafael Rego, Maria Farias, Victor Ivano Obesity Surgery.2025; 35(10): 4246. CrossRef
Metabolic Dysfunction Associated to Steatotic Liver Disease: A Review Janna Vanessa Diaz Torres, Vanessa Rocío Villanueva Guerrero, Jennifer Patricia Vargas Gómez, Fredy Javier Pacheco Miranda, Lorena Rocío Orozco Álvarez, Joseph David León Insignares, Marian Mares, Héctor Mario Rodríguez Ortiz, Evelyn Mendoza-Torres Metabolic Syndrome and Related Disorders.2025; 23(10): 427. CrossRef
Endoscopic Bariatric Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanistic Insights and Metabolic Implications Wissam Ghusn, Mira Sridharan, Rachel Fromer, Muhammet Ozdemir, Madeleine G. Haff, Eric J. Vargas Biomedicines.2025; 13(10): 2437. CrossRef
Huapeng Lin, Grace Lai-Hung Wong, Xinrong Zhang, Terry Cheuk-Fung Yip, Ken Liu, Yee Kit Tse, Vicki Wing-Ki Hui, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
Clin Mol Hepatol 2022;28(1):77-90. Published online November 5, 2021
Background/Aims We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients.
Methods The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals.
Result s: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57).
Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.
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