Excerpt from Caroli Disease

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Background

Caroli disease and Caroli syndrome are rare congenital disorders of the intrahepatic bile ducts. They are both characterized by dilatation of the intrahepatic biliary tree. The term Caroli disease is applied if the disease is limited to ectasia or segmental dilatation of the larger intrahepatic ducts. This form is less common than Caroli syndrome, in which malformations of small bile ducts and congenital hepatic fibrosis are also present. Caroli disease is sporadic, whereas Caroli syndrome is generally inherited in an autosomal recessive manner. As with congenital hepatic fibrosis, Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). A rare association with autosomal dominant polycystic kidney disease (ADPKD) has also been reported.

Pathophysiology

The precursor of the intrahepatic biliary tree is a double-layered sleeve of cells known as the ductal plate (DP). The DP first arises from hepatocyte precursors surrounding hilar portal vein vessels at 8 weeks gestation, and peripheral regions of the DP then develop sequentially. During the remainder of gestation, a process of DP remodeling occurs in which small areas of the double layer separate to form tubules, which join to form the intrahepatic biliary tree, while the remaining regions of the DP are lost, most likely through apoptosis. Caroli syndrome belongs to a subcategory of diseases thought to originate from failures of this process collectively known as ductal plate malformation.

In Caroli disease, abnormalities of the bile duct occur at the level of the large intrahepatic ducts (ie, left and right hepatic ducts, segmental ducts), resulting in dilatation and ectasia. Resulting biliary stasis may lead to cholelithiasis, cholangitis, and sepsis, as well as an increased risk of cholangiocarcinoma.

In Caroli syndrome, ductal plate malformation is present at the level of the smallest portal tracts and is associated with varying degrees of portal fibrosis. These findings are typical of congenital hepatic fibrosis; therefore, Caroli syndrome is thought to exist in the same spectrum of disease as congenital hepatic fibrosis. As with congenital hepatic fibrosis, the pathology may also include features of ARPKD.

Frequency

United States

Caroli disease and Caroli syndrome are very rare, with an estimated incidence of 1 case per 1,000,000 population. Caroli syndrome (ectasia of the large and small bile ducts with congenital hepatic fibrosis) is more common than Caroli disease (ectasia of only the large bile ducts).

Mortality/Morbidity

Patients with Caroli disease or syndrome may have recurrent episodes of cholangitis and are also at risk for associated bacteremia and sepsis.

• Patients with Caroli syndrome may have cholangitis, as do those with Caroli disease; however, they may also have the complications of portal hypertension observed in congenital hepatic fibrosis.
• Caroli syndrome is associated with ARPKD, and patients may have various degrees of renal cysts, interstitial fibrosis, and renal failure.
• Both Caroli disease and Caroli syndrome are associated with a risk of cholangiocarcinoma at a rate of 100 times that of the general population.

Sex

Symptoms of Caroli disease or syndrome are more common in female patients than in male patients.

Age

Symptoms appear first in adults, though childhood and neonatal cases have been reported. Cases of prenatal diagnosis based on ultrasonographic findings have been reported.

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