Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; and Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania
Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware; and Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania.
Pediatrics. 2018 Jan;141(1). 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.
进行性家族性胆汁淤积症 2 型是由胆汁盐输出泵 (BSEP) 的遗传缺失或活性降低引起的。BSEP 活性的降低或缺失导致胆汁盐排泄失败，导致胆汁盐在肝细胞中蓄积，随后发生肝损伤。临床上，患者出现黄疸，伴有严重的难治性瘙痒，并出现进行性肝功能障碍。当血清γ-谷氨酰转肽酶水平降低且伴有上述症状和体征时，通常是这种疾病的早期标志物。迄今为止的治疗选择包括肝移植和胆道分流术。我们报告了一种多药物治疗方案，包括 4-苯丁酸、奥卡西平和马拉利昔巴特（爱尔兰都柏林 Shire 制药公司的实验药物），该方案完全控制了 2 名部分 BSEP 活性丧失的兄弟姐妹的症状。
