Primary biliary cholangitis: current insights and novel therapies

Primary biliary cholangitis (PBC) may present asymptomatically or with potentially debilitating symptoms and can progress to cirrhosis despite first-line ursodeoxycholic acid (UDCA) therapy. A subset of patients exhibits inadequate response or intolerance, necessitating novel targeted approaches and a personalized management paradigm.

This review synthesizes recent literature on PBC, highlighting a new treatment approach centered on a finer prognostic characterization of patients at diagnosis and throughout follow-up. This approach enables the identification of high-risk phenotypes and variant forms, including PBC with autoimmune hepatitis features and premature ductopenic PBC which adversely influence UDCA responsiveness.We explore the mechanisms and efficacy of newly approved second-line therapies, and other emerging investigational agents. The urgent need for effective therapies for still difficult-to-treat symptoms such as pruritus and fatigue is also discussed.

The current PBC treatment paradigm necessitates a transition from reactive, failure-guided management toward prognostically based and individualized therapeutic regimens. Novel therapies hold the potential to enable more tailored clinical strategies, aiming for both robust biochemical responses and improved quality of life by alleviating symptom burden. Crucially, real-world evidence is essential for validating registrative trial findings and assessing long-term disease evolution, particularly in patient subgroups that are underrepresented within pivotal clinical trials.