Primary Biliary Cholangitis: The Evolving Therapeutic Landscape

Primary biliary cholangitis (PBC) is a progressive liver disease affecting the small intrahepatic bile ducts, specifically the interlobular and septal bile ducts, associated with an elevated alkaline phosphatase and positive anti-mitochondrial antibody on laboratory testing, which can lead to cirrhosis and the need for liver transplant. The goal of this review paper is to critically evaluate the current treatment algorithms for primary biliary cholangitis and propose future modifications. The first-line treatment option for PBC is ursodeoxycholic acid. FDA-approved second-line therapies are elafibranor and seladelpar. Off-label use of fenofibrate can also be considered. Traditionally, second-line therapies have been added after 12 months of treatment with ursodeoxycholic acid if the alkaline phosphatase and bilirubin levels are above desired goals. Evolving algorithms should consider earlier addition of second-line therapies at 6 months, especially in younger patients with increased liver stiffness, a goal of normalization of the alkaline phosphatase, and assessment of fatigue and pruritus in the decision about treatment options.