Primary biliary cholangitis and the narrowing gap towards optimal disease control

Although infrequent, primary biliary cholangitis is not indolent and remains a burdensome chronic autoimmune biliary disease. Progressive biliary injury and cholestasis results in complications of biliary cirrhosis, with reduced quality and quantity of life. Treatment advances beyond ursodeoxycholic acid and liver transplantation are notable, as efforts grow to prevent end-stage liver disease. Early identification of individuals at greatest risk for progression, in advance of cirrhosis, enhances treatment benefit. Intuitive care focuses on the best outcomes, such as biochemical control of disease (eg, normal alkaline phosphatase and bilirubin) and mitigation of symptoms (eg, pruritus). A multi-faceted approach to targeted therapeutic options is emerging to apply therapy beyond bile acid pool modification (ursodeoxycholic acid), including farnesoid X receptor agonism, peroxisome proliferator-activated receptor agonism, and ileal bile acid transporter inhibition. Obstacles to evaluating treatments include a prolonged clinical course, the difficulty in conducting long-term, placebo-controlled studies, and challenges in measuring quality of life effects. Generating robust, contemporaneous real-world evidence is therefore important in the primary biliary cholangitis space.