Bezafibrate therapy and biliary lipids: effects of short-term and long-term treatment in patients with various forms of hyperlipoproteinaemia.

Several hypolipidaemic drugs increase biliary cholesterol saturation and induce the formation of cholesterol gallstones. In order to determine the influence of bezafibrate, a clofibrate analogue with hypolipidaemic properties, on bile lipid composition, we studied twelve patients with various forms of hyperlipoproteinaemia (six type IIA, three type IIB and three type IV hyperlipoproteinaemia; six had a genetic diagnosis of familial hypercholesterolaemia and five familial combined hyperlipidaemia). After 4 weeks of therapy, when serum lipids were significantly reduced, the relative proportion of cholesterol in stimulated fasting duodenal bile was increased by 28% (P less than 0.001). Phospholipids were concomitantly increased and bile acids decreased, resulting in an increase in biliary cholesterol saturation from 89 +/- 4% to 105 +/- 8% (SEM, P less than 0.02). The changes induced were similar in patients with familial hypercholesterolaemia and familial combined hyperlipidaemia. After 1 year of continued treatment, serum lipid responses were unaltered. The changes in biliary lipids were also persistent as the relative cholesterol concentration remained increased by 33% (P less than 0.01) and cholesterol saturation averaged 106 +/- 8% (P less than 0.02). Although the effect on bile cholesterol appeared to be transient in some patients, the results of the present study suggest that the risk of cholesterol gallstone formation may be increased during bezafibrate therapy.