PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

Progressive familial intrahepatic cholestasis (PFIC), originally known as Byler's disease, was first described in an Amish kindred.8, 9 It is now known that there are several distinct phenotypes. In a general sense, PFIC is an inherited disorder of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period or the first year of life and leads to death from liver failure at ages ranging from infancy to adolescence. Cholangiograms show normal extra- and intrahepatic bile ducts. The pattern of affected children within families is consistent with an autosomal recessive inheritance. On the basis of clinical, biochemical, and histologic features, several studies have provided support for the heterogeneity of this clinical entity, suggesting the existence of different types caused by different disorders affecting the hepatocyte and related to defects of bile secretion or bile acid metabolism (Table 1)18, 19, 27, 29, 36, 44, 48, 49 Recent molecular and genetic studies have allowed the identification of genes responsible for three types of PFIC6, 7, 10, 16, 42, 43 and have shown that each form of PFIC is associated with mutations in hepatocellular transport system genes involved in bile formation (Fig. 1)23, 45 These findings now provide specific diagnostic tools for the investigation of children with PFIC. This article summarizes the molecular defects that are associated with PFIC and the proposed treatments. Liver diseases resembling PFIC that have recently been identified as inborn errors in primary bile acid synthesis are not be considered.19, 36