A Drug Regimen for Progressive Familial Cholestasis Type 2

Pediatrics. 2018 Jan;141(1):e20163877. doi: 10.1542/peds.2016-3877.


Progressive familial cholestasis type 2 is caused by a genetically determined absence or reduction in the activity of the bile salt export pump (BSEP). Reduction or absence of BSEP activity causes a failure of bile salt excretion, leading to accumulation of bile salts in hepatocytes and subsequent hepatic damage. Clinically, patients are jaundiced, suffer from severe intractable pruritus, and evidence progressive liver dysfunction. A low level of serum γ-glutamyl transpeptidase, when associated with the described signs and symptoms, is often an early identifier of this condition. Treatment options to date include liver transplantation and the use of biliary diversion. We report a multidrug regimen of 4-phenylbutyrate, oxcarbazepine, and maralixibat (an experimental drug owned by Shire Pharmaceuticals, Dublin, Republic of Ireland) that completely controlled symptoms in 2 siblings with partial loss of BSEP activity.

Publication types

  • Case Reports
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / genetics*
  • Benzothiepins / therapeutic use*
  • Biological Transport / genetics
  • Carbamazepine / analogs & derivatives
  • Carbamazepine / therapeutic use
  • Child
  • Cholestasis, Intrahepatic / complications
  • Cholestasis, Intrahepatic / diagnosis
  • Cholestasis, Intrahepatic / drug therapy*
  • Cholestasis, Intrahepatic / genetics*
  • Drugs, Investigational
  • Genetic Predisposition to Disease*
  • Glycosides / therapeutic use*
  • Humans
  • Male
  • Phenylbutyrates / therapeutic use*
  • Pruritus / drug therapy
  • Pruritus / etiology
  • Pruritus / physiopathology
  • Quality of Life
  • Recurrence
  • Risk Assessment
  • Siblings
  • Treatment Outcome


  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • Benzothiepins
  • Drugs, Investigational
  • Glycosides
  • Phenylbutyrates
  • oxcarbamazepine
  • Carbamazepine
  • 4-phenylbutyric acid
  • volixibat

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 2