Caroli disease is a congenital disorder characterized by multifocal, segmental dilatation of large intrahepatic bile ducts [1,2]. The condition is usually associated with renal cystic disease of varying severity. Caroli initially described two variants, which has led to some confusion in terminology.
- Caroli disease is the less common form and is characterized by bile ductular ectasia without other apparent hepatic abnormalities.
- The more common variant is Caroli syndrome, in which bile duct dilatation is associated with congenital hepatic fibrosis .
Caroli disease and syndrome have been described in the same family. Most cases are transmitted in an autosomal recessive fashion and are associated with autosomal recessive polycystic kidney disease (ARPKD). There have been rare cases occurring with autosomal dominant polycystic kidney disease .
The molecular pathogenesis of Caroli disease and syndrome is incompletely understood. The gene underlying ARPKD had been mapped to chromosome 6 (6p21-p12). The affected gene (called PKHD1 for polycystic kidney and hepatic disease 1) encodes for a large protein (4074 amino acids), which has been called fibrocystin to reflect the main structural abnormalities in liver and kidney . The protein shares structural features with the hepatocyte growth factor receptor, localizes to cilia, and appears to belong to a superfamily of proteins that are involved in the regulation of cell proliferation, and of cellular adhesion and repulsion [6,7]. It does not share any homology with the proteins responsible for autosomal dominant polycystic kidney disease. PKHD1 is expressed primarily in the kidneys with lower levels in liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. The genetic basis for the difference in Caroli disease and syndrome has not been defined.
Mutations in either of two different genes (PKD1 or PKD2) give rise to ADPKD, which, as mentioned above, has been associated with Caroli disease in rare instances. The protein products of the PKD genes (polycystin-1 and polycystin-2) are thought to interact as part of a multiprotein membrane-spanning complex involved in cell-cell or cell-matrix interactions [8,9]. Polycystin-1 is expressed in the fetal kidney and liver including the biliary system and is likely involved in the embryogenesis of these organs.