Pathophysiology, Clinical Manifestations, and Pharmacological Management of Pruritus in Primary Biliary Cholangitis: A Systematic Review

Abstract

Primary Biliary Cholangitis (PBC) is a chronic autoimmune cholestatic liver disease marked by the progressive destruction of small intrahepatic bile ducts. Chronic pruritus affects about 70-80% of patients, can greatly diminish quality of life, and does not present with primary skin lesions. Its pathogenesis is complicated, and the lack of primary lesion signs continues to make management a clinical challenge. This review aims to discuss the pathophysiology and the effectiveness of current pharmacological therapies for pruritus associated with PBC. Literature searches were carried out using PubMed and ScienceDirect, with keywords relating to PBC, pruritus, and treatment. Only original research articles in English published from 2016 to 2026 were included. In total, 29 studies met the inclusion criteria and were analyzed narratively. Pruritus in PBC involves several mediators, such as bile acids, autotaxin (ATX), lysophosphatidic acid (LPA), interleukin-31 (IL-31), and changes in gut microbiota. Clinically, cholestatic pruritus is usually worse at night, especially on the palms and soles, and occurs without primary skin lesions. Several pharmacological therapies have shown promising results, particularly seladelpar, bezafibrate, cholestyramine, rifampicin, nalfurafine, and inhibitors of the ileal bile acid transporter (IBAT). On the other hand, farnesoid X receptor agonists like obeticholic acid may worsen pruritus for some patients. Pruritus in PBC is a complex and multifactorial clinical problem. Treatments that target bile acid metabolism, the ATX-LPA pathway, pruritogenic cytokines, and the opioid system have shown potential to reduce pruritus intensity and improve quality of life for patients.