Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis.
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.
Nagasaka
Hironori
H
Division of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan.
Yorifuji
Tohru
T
Hirano
Kenichi
K
Ota
Akemi
A
Toyama-Nakagawa
Yumiko
Y
Takatani
Tomozumi
T
Tsukahara
Hirokazu
H
Kobayashi
Kunihiko
K
Takayanagi
Masaki
M
Inomata
Yukihiro
Y
Uemoto
Shinji
S
Miida
Takashi
T
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
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