J Gastroenterol Hepatol 1999 Jun;14(6):594-9

Progressive familial intrahepatic cholestasis

Jacquemin E
Department of Pediatrics and INSERM U 347, Bicetre Hospital, Le Kremlin Bicetre,
France

Abstract
Progressive familial intrahepatic cholestasis (PFIC), also known as Byler
disease, is an inherited disorder of childhood in which cholestasis of
hepatocellular origin often presents in the neonatal period and leads to death
from liver failure before adolescence. The pattern of appearance of affected
children within families is consistent with autosomal recessive inheritance.
Several studies have provided support for the heterogeneity of this clinical
entity suggesting the existence of different types due to different disorders
affecting the hepatocyte and related to defects of bile acid secretion or bile
acid metabolism. Recent molecular and genetic studies have identified genes
responsible for three types of PFIC and have shown that PFIC was related to
mutations in hepatocellular transport system genes involved in bile formation.
These findings now provide specific diagnostic tools for the investigation of
children with PFIC and should allow prenatal diagnosis in the future.
Genotype-phenotype correlations performed in patients treated with
ursodeoxycholic acid or biliary diversion should allow those PFIC patients who
could benefit from these therapies to be precisely identified. In the future,
other therapies, such as cell and gene therapies, might be considered and could
also represent an alternative to liver transplantation