biostudies-literatureSun WShandong Provincial Natural Science FoundationNational Key R&amp;D Program of ChinaNational Key R&D Program of ChinaNatural Science Foundation of Shandong ProvinceShandong Provincial Science Foundation for Youth ScholarsShandong Provincial key research and development program for major scientific and technological innovation1149-1156https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371309biostudies-literatureUnknown77(9)<h4>Objective</h4>The objective of this study was to evaluate and compare the risk of hepatotoxicity associated with the use of febuxostat and benzbromarone in patients with gout.<h4>Methods</h4>New users of febuxostat or benzbromarone with monitoring of liver function at least three times in a year after initiation of the study drugs were identified from an electronic medical record database. Propensity score matching (PSM) was performed between the two groups 1:1 matched for age, sex, and pretreatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Kaplan-Meier analysis was used to estimate the probability of hepatotoxicity (defined as ALT or AST > 3× upper limit of normal). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Subgroup analysis was performed based on age, body mass index, and comorbidities.<h4>Results</h4>A total of 2,338 patients with gout were eligible. A total of 37% of patients experienced Common Terminology Criteria for Adverse Events version 5 grades 1 to 3 for AST or ALT abnormality. After PSM, 488 febuxostat users were matched, with 488 participants receiving benzbromarone with a mean follow-up of 1.20 years. The incidence of hepatotoxicity was 39.6 and 16.8 per 1,000 person-years for febuxostat users and benzbromarone users, respectively. Febuxostat use was associated with a significantly greater risk of hepatotoxicity than benzbromarone (adjusted HR 2.75, 95% CI 1.28-5.91), especially in patients with elevated transaminases at baseline. Findings did not differ according to prespecified subgroups.<h4>Conclusion</h4>Febuxostat use is associated with a significantly greater risk of mild-to-moderate perturbation of liver function compared to benzbromarone in patients with gout.Arthritis care & researchRisk of Hepatotoxicity in Patients With Gout Treated With Febuxostat or Benzbromarone: A Propensity Score-Matched Cohort Study.PMC123713092021ZDSYS06#2022YFE0107600ZR2023MH2132021CXGC011103#2022YFC2503300ZR2023QH147Li XDalbeth NLi CCui LTerkeltaub RChen YSun WLiu TCheng XfalseRisk of Hepatotoxicity in Patients With Gout Treated With Febuxostat or Benzbromarone: A Propensity Score-Matched Cohort Study.<h4>Objective</h4>The objective of this study was to evaluate and compare the risk of hepatotoxicity associated with the use of febuxostat and benzbromarone in patients with gout.<h4>Methods</h4>New users of febuxostat or benzbromarone with monitoring of liver function at least three times in a year after initiation of the study drugs were identified from an electronic medical record database. Propensity score matching (PSM) was performed between the two groups 1:1 matched for age, sex, and pretreatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Kaplan-Meier analysis was used to estimate the probability of hepatotoxicity (defined as ALT or AST > 3× upper limit of normal). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Subgroup analysis was performed based on age, body mass index, and comorbidities.<h4>Results</h4>A total of 2,338 patients with gout were eligible. A total of 37% of patients experienced Common Terminology Criteria for Adverse Events version 5 grades 1 to 3 for AST or ALT abnormality. After PSM, 488 febuxostat users were matched, with 488 participants receiving benzbromarone with a mean follow-up of 1.20 years. The incidence of hepatotoxicity was 39.6 and 16.8 per 1,000 person-years for febuxostat users and benzbromarone users, respectively. Febuxostat use was associated with a significantly greater risk of hepatotoxicity than benzbromarone (adjusted HR 2.75, 95% CI 1.28-5.91), especially in patients with elevated transaminases at baseline. Findings did not differ according to prespecified subgroups.<h4>Conclusion</h4>Febuxostat use is associated with a significantly greater risk of mild-to-moderate perturbation of liver function compared to benzbromarone in patients with gout.2025-01-01T00:00:00Z2025 Sep2026-05-09T10:46:21.944Z2026-04-08T00:48:45.302ZS-EPMC123713094019567910.1002/acr.25547