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J Pediatr. 2014 May;164(5):1219-1227.e3. doi: 10.1016/j.jpeds.2013.12.032. Epub 2014 Feb 13.

Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2.

Author information

1
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
2
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. Electronic address: hayapi@mol.f.u-tokyo.ac.jp.
3
Department of Pediatrics, Dokkyo Medical University, Koshigaya Hospital, Saitama, Japan.
4
Department of Diagnostic Pathology, Kurume University Hospital, Fukuoka, Japan.
5
Bioscience Division, Reagent Development Department, TOSOH Corporation, Kanagawa, Japan.
6
Department of Pediatrics, Takarazuka City Hospital, Takarazuka-shi, Japan.
7
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
8
Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, RIKEN, Yokohama, Japan.
9
Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan.
10
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. Electronic address: kusuhara@mol.f.u-tokyo.ac.jp.

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.

PMID:
24530123
DOI:
10.1016/j.jpeds.2013.12.032
[Indexed for MEDLINE]

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