Ursodeoxycholic acid treatment in cholesterol gallstone disease: effects on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, biliary lipid composition, and plasma lipid levels

Abstract

The present study was undertaken to characterize the effects of ursodeoxycholic acid on biliary lipid metabolism in man. Fifteen gallstone patients were treated with ursodeoxycholic acid at a daily dosage of 15 mg per kg body weight for about 4 weeks before cholecystectomy. At operation a liver biopsy, together with gallbladder and hepatic bile, were obtained. Eighteen untreated gallstone patients undergoing cholecystectomy served as controls. During treatment with ursodeoxycholic acid, hepatic bile became unsaturated with cholesterol in all patients investigated. The total biliary lipid concentration remained unchanged. The hepatic cholesterol concentration decreased by about 20%. No significant change in the microsomal HMG CoA reductase activity was observed (38.5 +/- 6.7 pmol . min-1 . mg protein-1 vs 38.3 +/- 4.7 pmol . min-1 . mg protein-1 in the controls; means +/- SEM). Plasma concentrations of total cholesterol were reduced by about 10%, and those of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol by about 15%. Plasma triglyceride levels remained essentially unchanged during treatment. We conclude that, similar to chenodeoxycholic acid therapy, ursodeoxycholic acid treatment results in unsaturation of fasting hepatic bile. In contrast to the changes seen during chenodeoxycholic acid feeding, however, the unsaturation of hepatic bile during ursodeoxycholic acid treatment is not primarily related to a decreased hepatic HMG CoA reductase activity. Furthermore, while chenodeoxycholic acid tends to increase plasma LDL levels, such changes are not seen during ursodeoxycholic acid treatment.