Nobusuke Kishikawa1, Keishi Kanno1, Akiko Sugiyama1, Kenichi Yokobayashi1, Masafumi Mizooka1, Susumu Tazuma2. 1. Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 2. Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. stazuma@hiroshima-u.ac.jp.
Abstract
BACKGROUND: Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases. METHODS: Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed. RESULTS: Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients. CONCLUSIONS: Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.
BACKGROUND: Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases. METHODS: Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed. RESULTS: Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients. CONCLUSIONS: Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.
Authors: Osman Ahmed; Karin Littmann; Ulf Gustafsson; Camilla Pramfalk; Katariina Öörni; Lilian Larsson; Mirko E Minniti; Staffan Sahlin; German Camejo; Paolo Parini; Mats Eriksson Journal: J Am Heart Assoc Date: 2018-12-18 Impact factor: 5.501