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

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

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics
  • Cholestasis, Intrahepatic / complications
  • Cholestasis, Intrahepatic / drug therapy*
  • Cholestasis, Intrahepatic / genetics
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Genetic Markers
  • Homozygote
  • Humans
  • Infant
  • Liver Function Tests
  • Phenylbutyrates / therapeutic use*
  • Point Mutation
  • Pruritus / drug therapy*
  • Pruritus / etiology

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Gastrointestinal Agents
  • Genetic Markers
  • Phenylbutyrates
  • 4-phenylbutyric acid

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 2