Lipidome remodeling in primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease characterized by progressive destruction of intrahepatic bile ducts, impaired bile flow, and complex disturbances in bile acid and lipid metabolism. PBC is associated with a distinctive dyslipidemic profile, marked by elevated total cholesterol, accumulation of lipoprotein X, and paradoxically high HDL levels. At the molecular level, dysregulation of bile acid-activated nuclear receptors - particularly farnesoid X receptor (FXR) and peroxisome proliferator-activated receptors (PPARs) - contributes to abnormalities in cholesterol turnover, lipoprotein composition, and systemic metabolic signaling. Advances in lipidomics have revealed alterations in bioactive lipid classes such as sphingolipids and acylcarnitines, suggesting their role in hepatic inflammation and fibrogenesis. While ursodeoxycholic acid remains the standard of care, adjunctive therapies such as fibrates and selective nuclear receptor agonists are under investigation for their dual lipid-modifying and anti-cholestatic effects. A deeper understanding of lipid metabolism in PBC may yield novel biomarkers and guide more individualized therapeutic approaches.