{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:43:26Z","timestamp":1790649806855,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive cholestasis. Although ursodeoxycholic acid (UDCA) is the standard therapy, a substantial proportion of patients show inadequate response, highlighting the need for alternative or adjunct treatments. Fibrates have emerged as adjunct agents to UDCA, but evidence remains inconsistent across trials and meta-analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review of meta-analyses evaluating fibrates, alone or in combination with UDCA, in PBC patients. Databases were searched from inception to 2025. Primary outcomes included biochemical response (alkaline phosphatase [ALP] and bilirubin), treatment response rates, and adverse events. Overlap among meta-analyses was assessed using the corrected covered area (CCA), and methodological quality was evaluated with AMSTAR 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-three meta-analyses were included, encompassing 45 unique randomized controlled trials (RCTs) with a total of 3,276 patients after removing duplicate RCTs across meta-analyses. Combination therapy of fibrates with UDCA significantly improved biochemical outcomes compared with UDCA alone (ALP: MD \u221285.4\u00a0U\/L, 95% CI \u2212102.7 to \u221268.1; bilirubin: MD \u22120.45\u00a0mg\/dL, 95% CI \u22120.62 to \u22120.28). Biochemical response rates were higher with combination therapy (RR 1.42, 95% CI 1.25\u20131.61). Fibrate monotherapy showed moderate improvements in ALP (MD \u221248.7\u00a0U\/L, 95% CI \u221267.5 to \u221229.9) and bilirubin (MD \u22120.23\u00a0mg\/dL, 95% CI \u22120.39 to \u22120.07). Adverse events occurred in 12%\u201318%, mostly mild pruritus and gastrointestinal symptoms. Overlap between meta-analyses was high (CCA = 11%), and methodological quality ranged from moderate to high.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This umbrella meta-analysis provides the most comprehensive synthesis to date, supporting UDCA\u2013fibrate combination therapy for biochemical response in PBC. However, evidence on survival and transplant-free outcomes remains insufficient.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1797227","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:43:58Z","timestamp":1779684238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative efficacy and safety of ursodeoxycholic acid, fibrates, and combination therapy in primary biliary cholangitis: an umbrella meta-analysis of meta-analyses"],"prefix":"10.3389","volume":"17","author":[{"given":"Jian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Jinan Third People\u2019s Hospital","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital)","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Business Development, Shandong Provincial Third Hospital, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"489","DOI":"10.20524\/aog.2019.0403","article-title":"Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials","volume":"32","author":"Agrawal","year":"2019","journal-title":"Ann. 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