title: Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis.
abstract: No appropriate pharmaceutical therapy has been established for dyslipidemia with cholestasis in progressive familial intrahepatic cholestasis (PFIC)-1. We evaluated the efficacy of bezafibrate in PFIC-1. We monitored the clinical presentation and lipoprotein metabolism of 3 patients, aged 3, 4, and 8 years, with FIC1 deficiency, manifesting PFIC-1, over 12 months of bezafibrate therapy. Pruritus was substantially alleviated in the 3 patients after initiation of bezafibrate. Cholestasis was alleviated in 2 of them. Serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol increased 1.6- to 2.0-fold and 1.1- to 1.2-fold, respectively; but the values remained low and normal, respectively. Serum lipoprotein X, which was at normal levels before treatment, was elevated to levels above the upper limit of the reference range. High serum triglyceride levels decreased by 15% to 30%, to normal levels, after treatment initiation. The activities of lipoprotein lipase and hepatic triglyceride lipase were increased, but those of high-density lipoprotein regulators remained unchanged. Liver expression of multidrug resistance protein-3, which regulates lipoprotein X synthesis, was enhanced by bezafibrate therapy. Bezafibrate treatment favorably affected pruritus, dyslipidemia, and cholestasis in PFIC-1.
authors.affiliation: Division of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Akemi
authors.initials: A
authors.lastname: Ota
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyama-Nakagawa
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Takatani
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsukahara
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D001706:Biopsy; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol; C095122:multidrug resistance protein 3; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human; D001629:Bezafibrate