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.
Keywords: PPAR, bile acid, elafibranor, fibrosis, primary biliary cholangitis, seladelpar
Trends in molecular medicine
Journal Article
English
42285879
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