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J Pediatr ; 164(5): 1219-1227.e3, 2014 May.
Article in English | MEDLINE | ID: mdl-24530123

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.


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