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

Sotaro Naoi, Hisamitsu Hayashi, Takeshi Inoue, Ken Tanikawa, Koji Igarashi, Hironori Nagasaka, Masayoshi Kage, Hajime Takikawa, Yuichi Sugiyama, Ayano Inui, Toshiro Nagai, Hiroyuki Kusuhara

Index: J. Pediatr. 164(5) , 1219-1227.e3, (2014)

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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.Copyright © 2014 Elsevier Inc. All rights reserved.