Clofibrate treatment and bile cholesterol saturation: short-term and long-term effects and influence of combination with chenodeoxycholic acid.

Abstract

In order to determine whether the clofibrate-induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analysed from sixteen hyperlipoproteinaemic patients before and after 6 months to 2 years treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but two subjects cholesterol saturation remained elevated (150 +/- 7%, mean +/- SEM) compared to pretreatment values (112 +/- 6%, P less than 0.01). In nine of the patients, duodenal bile was obtained also after 6 weeks of treatment. Although two patients with increased saturation at 6 weeks displayed a return to basal values at 2 years, the majority showed no consistent changes between these two occasions. Addition of chenodeoxycholic acid to clofibrate medication led to a normalization of cholesterol saturation (from 145 +/- 9 to 89 +/- 18%, P less than 0.01) in eight out of nine patients studied. The serum levels of total cholesterol and triglycerides, very low density lipoprotein and high density lipoprotein cholesterol were not significantly changed. However, the low density lipoprotein (LDL) cholesterol concentration was increased by 15--20% (from 4.8 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P less than 0.01). It is concluded that clofibrate induces changes in biliary lipid composition which are consistent over at least 2 years of treatment. Possible measures to avoid these effects must therefore also be taken over a prolonged time. Chenodeoxycholic acid prevents the lithogenic effect of clofibrate but it cannot presently be recommended as an adjunct to clofibrate treatment since it simultaneously causes a rise in the serum concentration of LDL-cholesterol.