Hierro L, Jara P
Servicio de Hepatología y Trasplante, Hospital Infantil Universitario La Paz, Madrid, España.
Gastroenterol Hepatol. 2005 Aug-Sep;28(7):388-95. doi: 10.1157/13077760.
Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults.
确定参与胆汁分泌的转运系统以及编码这些系统的基因，已使大多数患病儿童的家族性肝内胆汁淤积症病因得以明确。ATP8B1基因突变导致FIC1（一种氨基磷脂翻转酶）功能缺陷，由于细胞膜脂质组成改变和核因子FXR表达降低，引发一系列不同的疾病，从进行性肝内胆汁淤积到良性复发性胆汁淤积。ABCB11基因突变导致胆小管胆汁盐输出泵（BSEP）功能缺陷，临床表现较早，儿童期可进展为肝细胞衰竭。ABCB4基因突变导致MDR3磷脂转运体改变，引发一系列不同的疾病，儿童期从进行性胆管损伤到肝硬化，成人期则表现为胆结石、妊娠期胆汁淤积或晚期肝硬化。
