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首页> 外文期刊>Clinics and research in hepatology and gastroenterology >Progressive familial intrahepatic cholestasis
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Progressive familial intrahepatic cholestasis

机译：进行性家族性肝内胆汁淤积

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Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and associated with mutations in hepatocellular transport-system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may arise later in infancy, in childhood or even during young adulthood. The main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due to defects in . ATP8B1 encoding the FIC1 protein and in . ABCB11 encoding bile salt export pump (BSEP) protein, respectively. Defects in . ABCB4, encoding multidrug resistance 3 protein (MDR3), impair biliary phospholipid secretion, resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests to exclude other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates for whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis may be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of liver tumors, especially in PFIC2 patients, should be offered from the first year of life. Hepatocyte transplantation, gene therapy and specific targeted pharmacotherapy may represent alternative treatments in the future.
机译：进行性家族性肝内胆汁淤积症（PFIC）是指儿童常染色体隐性疾病的异质性组，其破坏胆汁形成并表现为肝细胞性胆汁淤积。确切的发病率仍然未知，但是估计的发病率在1 / 50,000到1 / 100,000出生之间变化。已经鉴定出三种类型的PFIC，它们与参与胆汁形成的肝细胞转运系统基因的突变有关。 PFIC1和PFIC2通常出现在生命的头几个月，而PFIC3的发作可能在婴儿期，儿童期甚至成年期开始出现。主要临床表现包括胆汁淤积，瘙痒和黄疸。 PFIC患者通常在成年前会出现纤维化和终末期肝病。血清γ-谷氨酰转移酶（GGT）活性在PFIC1和PFIC2患者中正常，但在PFIC3患者中升高。 PFIC1和PFIC2都是胆汁盐分泌受损引起的。 ATP8B1编码FIC1蛋白和。 ABCB11分别编码胆盐输出泵（BSEP）蛋白。中的缺陷。编码多重耐药性3蛋白（MDR3）的ABCB4损害胆汁磷脂分泌，产生PFIC3。诊断的依据是临床表现，肝超声，胆道造影和肝组织学，以及排除了其他原因引起的儿童胆汁淤积的具体检查。 MDR3和BSEP肝免疫染色以及胆汁脂质成分分析应有助于选择可提出基因分型以确诊的PFIC候选者。对于已经鉴定出突变的受影响家庭，可以提出产前诊断。所有患者均应开始熊去氧胆酸（UDCA）治疗，以防止肝损害。在一些PFIC1和PFIC2患者中，胆道改道也可以缓解瘙痒和减慢疾病进展。但是，大多数PFIC患者最终都是肝移植的候选人。从出生的第一年起，应提供肝肿瘤的监测，尤其是PFIC2患者。肝细胞移植，基因治疗和特异性靶向药物治疗可能会在将来代表替代治疗。

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