Caroli Disease and Caroli Syndrome (CD and CS)

At a glance

A congenital disorder of nonobstructive, polycystic dilatation of intrahepatic bile ducts characterized by intrahepatic dilatation of the biliary tree, which may lead to cholangitis, cholelithiasis, portal hypertension, hepatic failure, and sepsis.

Synonyms

Congenital Intrahepatic Bile Duct Dilatation; Communicating Cavernous Ectasia of Intrahepatic Bile Ducts; Choledochal Cysts Type V (Todani classification). Caroli Disease (CD) is sometimes referred to as CD Type I and Caroli Syndrome (CS) as CD Type II.

History

The disorder bears the name of the French gastroenterologist Jaques Caroli (1902-1979) who, together with colleagues, described the disease in 1958. However, the first description is credited to the two English physicians H.R. Vachell and W. Mitchell Stevens, who in 1906 described a 52-year-old patient who died from what was most likely CD.

Incidence

Estimated to be in the range of 1:1,000,000. At least 400 cases have been described in the literature. CS is more common than CD (see “Clinical aspects” for differentiation). Both genders are equally affected.

Genetic inheritance

Not exactly known, but autosomal recessive inheritance has been suggested for both, CD and CS. Cases of CS with autosomal recessive polycystic kidney disease are associated with mutations in the PKHD1 (Polycystic Kidney and Hepatic Disease 1) gene located on chromosome 6p12.3-p12.2.

Pathophysiology

In CD, polycystic segmentation of the larger intrahepatic bile ducts (segmental, left, and right) occurs, whereas in CS the ductal abnormalities are more widespread and associated with hepatic fibrosis or even cirrhosis. Both forms are characterized by fibrosis of the portal tracts and seem to be caused by pathologic development in the formation of the ductal plate, which originates from hepatocytes surrounding the intrahepatic portal vein branches. Further differentiation during fetal life results in the formation of small tubules, which coalesce to form the intrahepatic biliary tree. Failure of the ductal plate to differentiate is summarized as ductal plate malformations. The structural anomaly of the intrahepatic bile ducts leads to nonobstructive, segmental, saccular or fusiform dilations and ectasia of the medium- and large-sized intrahepatic bile ducts with biliary stasis, hepato- and cholelithiasis, cholangitis with intrahepatic abscesses, and recurrent sepsis.

Diagnosis

CD/CS is a diagnosis of exclusion. Fetal ultrasound examination of liver and kidneys during pregnancy has resulted in prenatal diagnosis of CD/CS. However, further radiologic investigations (cholangiography, CT-imaging, or MRI-cholangiopancreatography), endoscopic retrograde cholangiopancreatography (ERCP; with high level of sensitivity), and liver biopsy may be required to confirm the diagnosis. The presence of communications between the cysts and the biliary tree is crucial for the diagnosis of CD. The “central dot sign” is considered to be pathognomonic for CD/CS and refers to the CT-appearance of the central fibrovascular bundle (consisting of portal vein and hepatic artery branches; ...