title: Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2.
abstract: To examine the effects of 4-phenylbutyrate (4PB) therapy in a patient with progressive familial intrahepatic cholestasis type 2. A homozygous c.3692G>A (p.R1231Q) mutation was identified in ABCB11. In vitro studies showed that this mutation decreased the cell-surface expression of bile salt export pump (BSEP), but not its transport activity, and that 4PB treatment partially restored the decreased expression of BSEP. Therapy with 4PB had no beneficial effect for 1 month at 200 mg/kg/day and the next month at 350 mg/kg/day but partially restored BSEP expression at the canalicular membrane and significantly improved liver tests and pruritus at a dosage of 500 mg/kg/day. We conclude that 4PB therapy would have a therapeutic effect in patients with progressive familial intrahepatic cholestasis type 2 who retain transport activity of BSEP per se.
authors: Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors: Sotaro
authors: S
authors: Naoi
authors: Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. Electronic address: hayapi@mol.f.u-tokyo.ac.jp.
authors: Hisamitsu
authors: H
authors: Hayashi
authors: Department of Pediatrics, Dokkyo Medical University, Koshigaya Hospital, Saitama, Japan.
authors: Takeshi
authors: T
authors: Inoue
authors: Department of Diagnostic Pathology, Kurume University Hospital, Fukuoka, Japan.
authors: Ken
authors: K
authors: Tanikawa
authors: Bioscience Division, Reagent Development Department, TOSOH Corporation, Kanagawa, Japan.
authors: Koji
authors: K
authors: Igarashi
authors: Department of Pediatrics, Takarazuka City Hospital, Takarazuka-shi, Japan.
authors: Hironori
authors: H
authors: Nagasaka
authors: Department of Diagnostic Pathology, Kurume University Hospital, Fukuoka, Japan.
authors: Masayoshi
authors: M
authors: Kage
authors: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors: Hajime
authors: H
authors: Takikawa
authors: Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, RIKEN, Yokohama, Japan.
authors: Yuichi
authors: Y
authors: Sugiyama
authors: Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan.
authors: Ayano
authors: A
authors: Inui
authors: Department of Pediatrics, Dokkyo Medical University, Koshigaya Hospital, Saitama, Japan.
authors: Toshiro
authors: T
authors: Nagai
authors: Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. Electronic address: kusuhara@mol.f.u-tokyo.ac.jp.
authors: Hiroyuki
authors: H
authors: Kusuhara
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002780:Cholestasis, Intrahepatic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007223:Infant; D008111:Liver Function Tests; D010654:Phenylbutyrates / Q000627:therapeutic use*; D017354:Point Mutation; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D005765:Gastrointestinal Agents; D005819:Genetic Markers; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid