Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: Reduced activity of cholesterol 7α-hydroxylase

Authors

  • Dagny Ståhlberg,

    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
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  • Eva Reihnér,

    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
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  • Mats Rudling,

    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
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  • Lars Berglund,

    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
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  • Kurt Einarsson,

    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
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  • Bo Angelin MD

    Corresponding author
    1. Metabolism Unit, Departments of Medicine, Surgery, and Clinical Chemistry, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden
    • Department of Medicine, Huddinge University Hospital, S-141 86 Huddinge, Sweden
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Abstract

Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7α-hydroxylasé activity was reduced by ≈60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7α-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy. (HEPATOLOGY 1995; 21:1025–1030.)

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