Advancing care in primary biliary cholangitis: emerging insights and novel therapies

Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease, is associated with fatigue and pruritus and can progress to cirrhosis if left untreated. Ursodeoxycholic acid (UDCA) has been the mainstay of therapy for over 40 years. However, 30-40% of PBC patients do not adequately respond to UDCA or have risk factors for disease progression and require second-line treatment.

Recent international cohort analyses have provided new insights that enable early identification of high-risk PBC patients and suggest that stricter treatment goals may lower mortality and reduce the need for liver transplantation. Alongside established second-line agents, several promising substances have progressed to phase 2 and 3 trials. Notably, seladelpar and elafibranor, two selective agonists of peroxisome proliferator-activated receptors, achieved high rates of biochemical response and good tolerability, leading to their recent approval for second-line treatment of PBC. Moreover, dedicated clinical trials addressed fatigue and pruritus, the two main symptoms of PBC.

Personalized treatment approaches for PBC are both feasible and essential to improve biochemical response, extend transplant-free survival and alleviate symptom burden. Well-tolerated novel therapies are poised to reshape the treatment landscape in the near future.