{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:38:30Z","timestamp":1791005910128,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate the efficacy and safety of novel oral anti-cholestatic agents for PBC. Methods: A systematic literature search was conducted in electronic databases up to September 2024. Randomized controlled trials, cohort studies, and case-control studies evaluating novel oral anti-cholestatic agents in adult PBC patients were included. The primary outcome was a change in alkaline phosphatase (ALP) levels. Safety was assessed by the incidence of serious adverse events. Random-effect meta-analyses were performed. Results: Ten studies involving 878 patients were analyzed. Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. The meta-analysis showed significant reductions in ALP levels with novel agents compared to the controls (SMD \u22122.80; 95% CI \u22123.56, \u22122.03; p &lt; 0.00001), with high heterogeneity (I2 = 93%). Saroglitazar achieved the largest effect size. There was no significant difference in serious adverse events between novel agents and controls (OR 1.21; 95% CI 0.81, 1.83; p = 0.35). Conclusions: Novel oral anti-cholestatic agents show promise in improving biochemical markers in PBC patients with suboptimal UDCA responses, with a safety profile comparable to controls. However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety.<\/jats:p>","DOI":"10.3390\/ph18050697","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T11:37:02Z","timestamp":1746704222000},"page":"697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and Safety of Novel Oral Anti-Cholestatic Agents for Primary Biliary Cholangitis: Meta-Analyses and Systematic Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-1611","authenticated-orcid":false,"given":"Eyad","family":"Gadour","sequence":"first","affiliation":[{"name":"Multiorgan Transplant Centre of Excellence, Liver Transplant Unit, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia"},{"name":"Department of Medicine, Zamzam University College, Khartoum 11113, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5336-5789","authenticated-orcid":false,"given":"Bogdan","family":"Miutescu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Advanced Regional Research Centre in Gastroenterology and Hepatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Bashir","sequence":"additional","affiliation":[{"name":"Gastroenterology, Yas Clinic Abu Dhabi Stem Cell Center, Abu Dhabi SE44, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abubaker","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicine, King Abdulaziz National Guard Hospital, Ahsa 36428, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Alanzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, King Abdulaziz National Guard Hospital, Ahsa 36428, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9280-5989","authenticated-orcid":false,"given":"Abdullah A.","family":"Al-Shahrani","sequence":"additional","affiliation":[{"name":"Gastroenterology, King Khalid University, Abha 62521, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymen","family":"Almuhaidb","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahed","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Abaalkhail","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11211, Saudi Arabia"},{"name":"Department of Liver and Small Bowel Transplantation and Hepatobiliary-Pancreatic Surgery, King Faisal Specialist Hospital and Resesarch Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0892-0931","authenticated-orcid":false,"given":"Hadi","family":"Kuriry","sequence":"additional","affiliation":[{"name":"Multiorgan Transplant Centre of Excellence, Liver Transplant Unit, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Saad","family":"AlQahtani","sequence":"additional","affiliation":[{"name":"Multiorgan Transplant Centre of Excellence, Liver Transplant Unit, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia"},{"name":"Department of Surgery, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Trivella, J., John, B.V., and Levy, C. 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