Bile Acids and Cholestatic Liver Disease 1: Primary Biliary Cholangitis (PBC)

Abstract

Primary biliary cholangitis (PBC), formally known as primary biliary cirrhosis and recently the name was changed with keeping the abbreviation “PBC” along with a global consensus, is a chronic cholestatic liver disease, potentially resulting in liver failure. While the aspect of autoimmune disease of PBC was formally emphasized and immune reactions with lymphocytes against autoantigens were extensively investigated, the interactions between bile acids and cholangiocytes have been well clarified in this decade. Cytotoxic hydrophobic bile acids play an important role in pathogenesis of PBC via defect in the biliary HCO3− “umbrella.” This biliary HCO3− “umbrella” is maintained by Cl−/HCO3− exchanger (anion exchanger 2 (AE2)) located at apical surface of cholangiocytes, and accumulating evidences have indicated that lack or reduction of AE2 activities is closely associated with PBC. Treatment is targeted to cytotoxicity of hydrophobic bile acids; ursodeoxycholic acid (UDCA) exerts its effect through reduction of cytotoxicity of hydrophobic bile acids and stabilizing biliary HCO3− umbrella. Both bezafibrate and obeticholic acids are also capable of reducing cytotoxicity of hydrophobic bile acids. The alternative treatment is strongly awaited for patients with PBC refractory to UDCA, and targeting cytotoxicity of hydrophobic bile acids, as well as immune-based therapies, is expected to be a promising approach for new pharmacotherapy.