{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:40:58Z","timestamp":1792622458225,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH213"],"award-info":[{"award-number":["ZR2023MH213"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["#2022YFC2503300"],"award-info":[{"award-number":["#2022YFC2503300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["#2022YFE0107600"],"award-info":[{"award-number":["#2022YFE0107600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010Meier analysis was used to estimate the probability of hepatotoxicity (defined as ALT or AST &gt; 3\u00d7 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010up of 1.20 years. The incidence of hepatotoxicity was 39.6 and 16.8 per 1,000 person\u2010years 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\u20135.91), especially in patients with elevated transaminases at baseline. Findings did not differ according to prespecified subgroups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Febuxostat use is associated with a significantly greater risk of mild\u2010to\u2010moderate perturbation of liver function compared to benzbromarone in patients with gout.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr25547-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.25547","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T02:46:25Z","timestamp":1744080385000},"page":"1149-1156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Risk of Hepatotoxicity in Patients With Gout Treated With Febuxostat or Benzbromarone: A Propensity Score\u2013Matched Cohort Study"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3566","authenticated-orcid":false,"given":"Wenyan","family":"Sun","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Cui","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-7473","authenticated-orcid":false,"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinde","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University and Institute of Metabolic Diseases, Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-4476","authenticated-orcid":false,"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-3731","authenticated-orcid":false,"given":"Changgui","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University and Institute of Metabolic Diseases, Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1166"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2100028"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i13.1717"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200831080-00002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358-019-0080-x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2011.622732"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42266"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009741003742797"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13266"},{"issue":"28","key":"e_1_2_6_11_1","article-title":"Egyptian consensus on treat\u2010to\u2010target approach of gout: evidence\u2010based clinical practice guidelines for the management of gout","volume":"49","author":"El Miedany Y","year":"2022","journal-title":"Egypt Rheumatol Rehabil"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28403"},{"key":"e_1_2_6_13_1","unstructured":"National Institutes of Health and LiverTox.Drug record: Febuxostat. 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