Caroli's disease

Overview
Vachel and Stevens were the first to describe a case of cystic dilatation of the intrahepatic bile ducts in 1906, but Jacques Caroli in 1958 gave a more thorough description of a syndrome of congenital malformation of the intrahepatic ducts with segmental cystic dilatation, increased biliary lithiasis, cholangitis and liver abscesses, associated with renal cystic disease or tubular ectasia. The disease is uncommon, with about 180 cases reported in the literature.

Epidemiology and Demographics
Biliary cysts are more common in Japan and in young women.

Biliary Cysts

 * Biliary cysts have been described throughout the biliary system, and are classified according to their location and anatomy.
 * Many biliary cysts are congenitally acquired, perhaps as a consequence of unequal proliferation of epithelial cells during embryonic biliary duct development. Some biliary cysts are acquired, and some may develop in association with anatomic variations that lead to abnormally high ductal pressures in association with other predisposing factors.
 * Type I (75-85%)
 * Choledochal cysts - cystic dilatation of the common bile duct (CBD)
 * Often presents during infancy with significant liver disease.
 * Type II (2-3%)
 * Diverticulae anywhere in the extrahepatic ducts.
 * Presenting symptoms’s may reflect cystic compression of nearby structures.
 * Type III (1-5%)
 * Choledochocele cysts
 * Often present with pain and obstructive jaundice; many have pancreatitis.
 * Type IV (18-20%)
 * IVA – Multiple cysts in the Intra- and Extra-hepatic ducts
 * IVB – Multiple cysts in the Extra-hepatic ducts only
 * Type V – Caroli’s Disease - rare
 * Single or Multiple Intrahepatic bile duct cysts

Caroli's Disease

 * Two subtypes of Caroli's disease have been described:
 * Simple type
 * As classically described, without cirrhosis or portal HTN
 * 60-80% associated with medullary sponge kidney
 * Periportal fibrosis type
 * Also associated with:
 * Congenital hepatic fibrosis – bland portal fibrosis, hyperproliferation of interlobular bile ducts within the portal areas, with variable shapes and size of bile ducts, and preservation of normal lobular architecture.
 * Cirrhosis
 * Portal hypertension (HTN)
 * Esophageal varices
 * Renal cystic lesions also often occur
 * Hepatic function is preserved in most, but many patients have recurrent cholangitis, liver abscesses and portal HTN.
 * The cysts are nonobstructive saccular or fusiform dilatations of the intrahepatic ducts.
 * The disease may be unilobar or bilobar. Unilobar disease is most commonly localized to the left lobe of the liver.
 * Some reviews have reported that pure Caroli’s disease is not that common, and more patients actually have Type IVA disease, with both intra- and extra-hepatic cysts.
 * Intrahepatic biliary cystic disease should be differentiated from polycystic liver disease, an autosomal dominant disorder characterized by cystic collections of serous fluid not in communication with the biliary tree.
 * The incidence of malignant transformation in intrahepatic cysts is ~7% in Caroli’s disease.

Clinical Characteristics

 * Relatively uncommon, with equal prevalence in men and women.
 * Autosomal dominant familial inheritance of Caroli’s disease has been described in one family with autosomal dominant polycystic kidney disease. Autosomal recessive inheritance has also been described.


 * Patients often present in young adulthood
 * 80% present before 30 years of age.


 * Cholangitis
 * Patients often present with recurrent episodes of fever/chills and abdominal pain due to cholangitis.


 * Biliary lithiasis
 * Occurs in about a third.


 * Portal HTN and Varices
 * Occasionally patients will present later in life with sequelae of liver disease and portal HTN.


 * Ductal rupture
 * Has been described with intrahepatic as well as extrahepatic bile duct cysts. This can result in peritonitis.
 * Liver abscess
 * Can occur in association with the intrahepatic cysts, abnormal biliary flow, cholangitis, and/or stone disease.


 * Malignancy
 * Is more common in the affected tissues, including cancer of the gall bladder, biliary tree, and liver.
 * This often occurs in patients ~50 years of age, about 2 decades before the mean age of carcinoma in the general population, and at a much higher rate (~7%) than the general population.
 * The reason for this increase in carcinoma is not clear, but may occur in association with pancreatic/biliary regurgitation.
 * Removal of cysts does not necessarily reduce the risk.
 * Once malignancy develops, prognosis is dismal.


 * Renal tubular ectasia or renal cystic disease
 * More common in these patients.

MRI and CT

 * Abdominal CT scans are also often diagnostic.

Echocardiography or Ultrasound

 * Ultrasound is often adequate for the diagnosis of biliary cysts, except for Type III choledochoceles. Biliary cysts can often even be picked up in utero.

Other Imaging Findings

 * Cholescintigraphy (HIDA) scans are also quite useful for all but Type III choledochoceles. Findings include biliary tract dilatation and tracer retention after 24 hours.  It gives data on excretory function, which is also useful post surgical repair.
 * Endoscopic Retrograde Cholangio-Pancreatography (ERCP) provides excellent visualization.
 * ERCP is particularly useful for type III choledochoceles, demonstrating a clubbed distal common bile duct (CBD) and a round, cyst-like, contrast-filled structure in the terminal CBD often extending into the duodenal lumen.
 * Magnetic resonance cholangiopancreatography (MRCP) is also a available for evaluation.

Differential Diagnosis

 * Biliary cysts are often not listed in the differential diagnosis of biliary obstruction (note their conspicuous absence from my report on cholangitis), so they are often not thought of until they are found at surgery or during imaging procedures.

Treatment

 * Intrahepatic biliary cyst treatment depends on degree of involvement.
 * Segmental disease can be potentially cured with lobectomy. The risks and benefits of undergoing this surgery, versus the associated risks of future cholangitis, stone disease, pancreatitis, and liver abscess if not treated surgically have to be weighed in individual patients.
 * If both lobes are involved, surgical resection may not be an option.
 * If patients have recurrent cholangitis, a trial of prophylactic antibiotics could be considered.
 * Liver transplant is a final option.
 * Cholecystectomy is indicated because it reduces the likelihood of cholangitis, and because the gallbladder is at increased risk of malignancy in patients with biliary cysts.
 * A report in the Lancet describes a significant improvement in stone disease in Caroli’s disease patients treated with ursodeoxycholic acid (Actigall) 10-20 mg/kg/d.
 * Extrahepatic biliary cysts are often treated with surgical repair due to risks of cyst rupture with secondary peritonitis, cholangitis and liver cirrhosis.
 * Surgical options include primary cyst excision, and internal drainage procedures, such as choledochoduodenostomy and Roun-en-Y choledochojejunostomy. The down sides of internal drainage include a high complication rate and risk of malignancy in the abnormal region (2.5%).