High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that results in progressive fibrosis of intrahepatic and extrahepatic bile ducts. No effective therapy currently exists for this disease. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is the most promising treatment option because of its benign side effect profile and documented benefit in the treatment of other cholestatic liver diseases, including primary biliary cirrhosis. Multiple studies using standard-dosage (8-15 mg/kg/d) and high-dosage (20-30 mg/kg/d) UDCA generally show improvement in liver chemistries in PSC patients, and several show improvement in liver histology. However, the majority of trials using UDCA in PSC are underpowered and fail to show improvements in clinically relevant endpoints, such as delayed progression to cirrhosis, portal hypertension, liver transplantation, development of cholangiocarcinoma, or death.