Laboratory Studies
Bilirubin levels are usually in the reference range in patients with Caroli disease or Caroli syndrome.
Transaminase levels may be slightly elevated.
The CBC count may reveal thrombocytopenia and leukopenia if portal hypertension and hypersplenism are present. An elevated WBC count or erythrocyte sedimentation rate (ESR) may indicate cholangitis.
Coagulation profile may reveal a coagulopathy secondary to cholestasis and vitamin K malabsorption or due to poor hepatic synthetic function.
Creatinine and BUN values should be obtained to detect associated renal disease.
Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are used to screen for cholangiocarcinoma. [5]
Imaging Studies
Ultrasonography is the best initial imaging study because it reveals the irregular dilatation of the large intrahepatic bile ducts typical of Caroli disease or Caroli syndrome. Extrahepatic biliary dilatation may also be present as a result of prior cholelithiasis. Doppler evaluation of the liver can be used to detect portal hypertension. The kidneys can also be assessed for evidence of polycystic kidney disease.
Magnetic resonance cholangiography is increasingly used to diagnose Caroli disease or Caroli syndrome. It provides excellent images of the intrahepatic and extrahepatic biliary trees and can also depict renal involvement. Its use is currently limited by the availability of the necessary equipment and expertise.
CT may be used, particularly if ultrasonography cannot be performed because of bowel gas or body habitus. It can reveal multiple cystic dilatations of the intrahepatic bile ducts. The central dot sign involves enhancing dots within the dilated intrahepatic bile ducts, representing portal radicles. [4]
Hepatobiliary scintigraphy can be useful to document communication between cysts and the biliary system, a feature present in Caroli disease or Caroli syndrome but absent in polycystic liver disease and hepatic abscesses.
Invasive modalities, such as percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP), enable excellent visualization of the biliary tree. ERCP can also be of therapeutic use for stone extraction, sphincterotomy, or biliary stenting.
Procedures
Blood culture should be performed in cases of suspected chronic cholangitis.
When obtained in Caroli syndrome, liver biopsy shows bands of mature fibrosis tissue and distorted bile ducts characteristic of congenital hepatic fibrosis.
ERCP has been used to identify and treat biliary stones in patients with Caroli disease or Caroli syndrome but is associated with postprocedural risks, including pancreatitis or cholangitis.
Portosystemic shunting may be indicated in patients who have portal hypertension.
Histologic Findings
In Caroli syndrome, the liver biopsy reveals typical findings of ductal plate (DP) malformation, with ducts arranged in a circumferential pattern around the portal vein branches and with a variable degree of associated portal fibrosis.
In Caroli disease, only large intrahepatic ducts are affected, without associated hepatic fibrosis.
Other Tests
The identification of the PKHD1 gene in patients with autosomal recessive polycystic kidney disease (ARPKD) has provided a basis for gene-based diagnostic testing. Several studies have analyzed PKHD1 and have reported more than 300 mutations, with the mutation detection rate varying 42-87%. [6]
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Hepatic ultrasonogram of a neonate with Caroli disease. Multiple dilated intrahepatic bile ducts are present. Courtesy of Richard Bellah, MD, The Children's Hospital of Philadelphia.
