title: Long-term administration of a Niemann-Pick C1-like 1 inhibitor, ezetimibe, does not worsen bile lithogenicity in dyslipidemic patients with hepatobiliary diseases.
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.
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Kishikawa
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Kanno
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugiyama
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yokobayashi
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Mizooka
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. stazuma@hiroshima-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001646:Bile / Q000737:chemistry; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood; D050171:Dyslipidemias / Q000503:physiopathology*; D000069438:Ezetimibe / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005234:Fatty Liver / Q000150:complications*; D005260:Female; D042882:Gallstones / Q000150:complications*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage
chemical_list: D000924:Anticholesteremic Agents; D008074:Lipoproteins; D010840:Phytosterols; C030104:lipoprotein cholesterol; C021273:campesterol; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D000069438:Ezetimibe
keywords: Bile lithogenicity; Cholecystectomy; Ezetimibe; Niemann-Pick C1-like 1; Ursodeoxycholic acid