Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones

Background and Aims: There is limited information available on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on hepatic an d biliary cholesterol metabolism in patients with gallstones. The aims of t his study were to determine the effect of simvastatin on the regulatory ele ments of cholesterol metabolism that determine the concentrations of choles terol in plasma and bile. Methods: Thirty-one gallstone patients were enrolled in the study; 17 were treated with 20 mg simvastatin daily for 3 weeks prior to cholecystectomy a nd 14 served as controls. Samples of blood, liver, gall-bladder bile and bi le from the common bile duct (CBD) were collected and analysed. Results: The plasma cholesterol (-30%), triacylglycerol (-23%) and low-dens ity lipoprotein (LDL) cholesterol (-42%) concentrations were significantly lowered by simvastatin treatment, as was the plasma lathosterol: cholestero l (-70%), which reflects whole-body cholesterol synthesis. Despite these ch anges, the hepatic LDL receptor protein and LDL receptor activity in circul ating mononuclear cells were similar in both groups. There were no differen ces in the plasma phytosterol: cholesterol, which reflects the intestinal c holesterol absorption capacity or in the activity of hepatic acyl-coenzyme A: cholesterol acyltransferase. There were however, lower cholesterol conce ntrations in CBD (-68%) and gall bladder (-41%) bile, and decreased lithoge nic (-47%) and bile acid hydrophobicity (-22%) indices of CBD bile in the s imvastatin group. Conclusions: These data indicate that simvastatin reduced plasma and biliar y cholesterol levels primarily by reducing cholesterol synthesis. The reduc tion in CBD bile lithogenicity and bile acid hydrophobicity by simvastatin suggests that this agent may be useful for people who have early stages of cholesterol gallstone development and in whom a choleretic effect is requir ed. (C) 2000 Blackwell Science Asia Pty Ltd.