PubMed:10223112 JSONTXT 5 Projects

[Progressive familial intrahepatic cholestasis and hereditary anomalies lf hepatocellular metabolism of bile acids]. Cholestases intrahépatiques fibrogènes familiales et anomalies héréditaires du métabolisme hépatocytaire des acides biliaires. Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited cholestasis of hepatocellular origin which is characterized by cholestasis presenting often in the neonatal period leading to death due to liver failure at ages ranging from infancy to adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. The etiology is poorly understood but several studies have recently provided support for an heterogeneity with at least three subcategories among the spectrum of PFIC. The first subtype is characterized by an early onset, often during the neonatal period, a severe pruritus, normal serum gamma-glutamyltransferase (GGT) activity and cholesterol level, high concentration of serum primary bile acids, absence or very low levels of primary bile acids, absence or very low levels of primary bile acids in bile, and absence of ductular proliferation on standard optical liver histology. Its leads to death due to liver failure within a few years, rarely after adolescence. It is possibly due to an inborn error in primary bile acid secretion and recently, a locus for this subtype has been mapped in the original Byler pedigree to 18q21-q22, the benign recurrent intrahepatic cholestasis region. In the second subtype, affected children exhibit also normal serum GGT activity and cholesterol level and absence of ductular proliferation, but have no pruritus and only traces of primary bile acids in serum. An inborn error in primary bile acid synthesis has been demonstrated in this subtype. The third subtype presents later in life, carries a higher risk of portal hypertension and gastrointestinal bleeding and ends in liver failure at a later age. It is characterized by a mild and unconstant pruritus, high GGT serum activity, moderately raised concentrations of serum primary bile acids, normal concentration of biliary primary bile acids, and ductular proliferation and inflammatory infiltrate with patency of intra and extrahepatic bile ducts. An abnormal expression of the MDR3 gene is involved. A fair proportion of children affected with all subtypes of PFIC may benefit from oral bile acid therapy. In some cases partial external biliary diversion or liver transplantation should be proposed.