Gallstone dissolution therapy with ursodiol

Abstract

The balance between the synthesis of cholesterol and bile acids in the liver is a key factor in the formation of gallstones. Patients with cholesterol gallstones have been shown to have higher rates of hepatic cholesterol synthesis and lower rates of bile acid synthesis than control subjects, as measured by the activity of the respective rate-controlling enzymes. Treatment with ursodiol reduced the high levels of hydroxymethylglutaryl coenzyme A reductase in gallstone patients treated for approximately one year. Such treatment did not appear to inhibit endogenous synthesis of bile acids. Ursodiol is distinct from chenodeoxycholic acid in that no significant abnormalities of liver function have been reported during its use. Bacterial 7-dehydroxylation is more active for chenodeoxycholic acid than ursodiol; thus less lithocholic acid is formed with ursodiol. Patients receiving the highest dose of ursodiol often have been shown to have the lowest percentage of lithocholic acid in the bile. During treatment with ursodiol for dissolution of gallstones, symptoms of biliary distress began to improve after three to six weeks. Gallstones will recur in about 50% of patients, but no consensus exists on management of patients after dissolution of their stones. Overall, ursodiol is a safe and effective litholytic agent.