AISF practice guidance on the treatment of primary biliary cholangitis: A 2026 update

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease that, if untreated or inadequately treated, may progress to advanced fibrosis, cirrhosis, and liver-related complications. Although ursodeoxycholic acid (UDCA) remains the cornerstone of first-line therapy and improves transplant-free survival, an important proportion of patients show an inadequate biochemical response, and many continue to experience substantial symptoms, particularly pruritus and fatigue, with a major impact on quality of life. In recent years, the therapeutic landscape of PBC has evolved following the withdrawal of obeticholic acid and the availability of selective PPAR agonists, including elafibranor and seladelpar. At the same time, disease management has shifted beyond a dichotomous definition of biochemical response toward a risk-based and holistic approach integrating biochemical response, fibrosis stage, liver stiffness, and patient-reported outcomes. Therapeutic targets should be individualized according to age, disease stage, symptom burden, and risk of progression, distinguishing between "adequate" and "complete" biochemical response and supporting earlier treatment escalation in high-risk and symptomatic patients. This updated AISF guidance provides an evidence-based framework for PBC management in 2026 and beyond, reviewing therapeutic goals, response criteria, second-line therapies, and management in specific settings, including cirrhosis, pregnancy, variant syndromes, and metabolic comorbidities, emphasizing a patient-centred approach and highlighting unmet needs and future directions.