Breaking the metabolo-immune cycle in primary biliary cholangitis for therapeutic benefit.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis-driven bile duct injury and fibrosis. Biliary epithelial cells (BECs) play a central role in both bile homeostasis and immune regulation, and their metabolic and immune dysfunction is critical in PBC pathogenesis. Furthermore, systemic metabolic disturbances, such as gut dysbiosis, contribute to disease progression. This paper systematically examines the interplay between BEC metabolism-including bile acid imbalance and lipotoxicity-and immune dysregulation, such as autoantigen exposure and Th1/Th17 responses, highlighting how these interactions fuel a self-sustaining "metabolo-immune-fibrosis" cycle in PBC. Current and emerging therapies are also reviewed, emphasizing that future management should move beyond single-pathway targeting and pursue combination strategies capable of simultaneously modulating metabolic, inflammatory, and immune networks.