Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
J Pediatr. 2014 May;164(5):1219-1227.e3. doi: 10.1016/j.jpeds.2013.12.032. Epub 2014 Feb 13.
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.
研究 4-苯丁酸（4PB）治疗进行性家族性肝内胆汁淤积症 2 型患者的效果。在 ABCB11 中发现了一个纯合 c.3692G>A（p.R1231Q）突变。体外研究表明，该突变降低了胆汁盐输出泵（BSEP）的细胞表面表达，但不影响其转运活性，而 4PB 治疗部分恢复了 BSEP 的减少表达。以 200mg/kg/天治疗 1 个月和以 350mg/kg/天治疗下一个月无明显效果，但以 500mg/kg/天的剂量治疗时，部分恢复了胆小管膜上的 BSEP 表达，并显著改善了肝功能和瘙痒。我们的结论是，对于保留 BSEP 转运活性的进行性家族性肝内胆汁淤积症 2 型患者，4PB 治疗将具有治疗效果。
