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

Abstract

There is limited information available on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on hepatic and biliary cholesterol metabolism in patients with gallstones. The aims of this study were to determine the effect of simvastatin on the regulatory elements of cholesterol metabolism that determine the concentrations of cholesterol in plasma and bile. Thirty-one gallstone patients were enrolled in the study; 17 were treated with 20 mg simvastatin daily for 3 weeks prior to cholecystectomy and 14 served as controls. Samples of blood, liver, gall-bladder bile and bile from the common bile duct (CBD) were collected and analysed. The plasma cholesterol (-30%), triacylglycerol (-23%) and low-density lipoprotein (LDL) cholesterol (-42%) concentrations were significantly lowered by simvastatin treatment, as was the plasma lathosterol: cholesterol (-70%), which reflects whole-body cholesterol synthesis. Despite these changes, the hepatic LDL receptor protein and LDL receptor activity in circulating mononuclear cells were similar in both groups. There were no differences in the plasma phytosterol: cholesterol, which reflects the intestinal cholesterol absorption capacity or in the activity of hepatic acyl-coenzyme A: cholesterol acyltransferase. There were however, lower cholesterol concentrations in CBD (-68%) and gall bladder (-41%) bile, and decreased lithogenic (-47%) and bile acid hydrophobicity (-22%) indices of CBD bile in the simvastatin group. These data indicate that simvastatin reduced plasma and biliary cholesterol levels primarily by reducing cholesterol synthesis. The reduction 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 required.