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The emerging role of PPARs in primary biliary cholangitis
Xavier Palomer1, Ricardo Rodríguez-Calvo2, Sandra García-Mateo3
1Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, 08028 Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain; Pediatric Research Institute, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain.
None:
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts, leading to fibrosis, cirrhosis, and liver failure. Ursodeoxycholic acid remains the first-line treatment, but up to 40% of patients respond inadequately and continue to experience fatigue and pruritus. This therapeutic gap has recently been addressed by the approval of two new drugs, elafibranor and seladelpar, which activate peroxisome proliferator-activated receptors (PPARs). This review explores recently unveiled molecular mechanisms underlying the effectiveness of PPAR-targeting drugs in PBC, focusing on their effects on cellular immune regulation, bile acid production and toxicity, and hepatic fibrosis. Additionally, we examine current knowledge and ongoing challenges that will influence the roles of PPAR agonists in improving PBC treatment.
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