Caroli disease

Overview

Caroli disease is a rare congenital disorder characterized by segmental, non-obstructive dilatation of the large intrahepatic bile ducts. It is considered a type of ductal plate malformation and is part of a spectrum that also includes Caroli syndrome, which combines bile duct dilatation with congenital hepatic fibrosis. Caroli disease can lead to complications such as recurrent cholangitis (bile duct infections), gallstones, and an increased risk of bile duct cancer (cholangiocarcinoma). The condition is typically diagnosed in childhood or early adulthood.

Causes

Caroli disease is believed to be caused by developmental anomalies of the ductal plate during embryogenesis. The exact mechanism is not fully understood, but it is associated with genetic mutations, particularly in the PKHD1 gene, which is also implicated in autosomal recessive polycystic kidney disease (ARPKD). The condition may occur sporadically or be inherited in an autosomal recessive pattern. When combined with hepatic fibrosis and kidney involvement, it is referred to as Caroli syndrome.

Symptoms

The symptoms of Caroli disease vary in severity and may be absent until complications arise. Common clinical features include:

• Recurrent right upper abdominal pain

• Recurrent episodes of cholangitis: Fever, chills, jaundice, and abdominal pain

• Hepatomegaly: Enlarged liver in some patients

• Jaundice: Yellowing of the skin and eyes due to bile duct obstruction or infection

• Gallstones: Frequently develop in the dilated bile ducts

• Portal hypertension: In Caroli syndrome due to associated liver fibrosis

• Failure to thrive or growth issues in children with severe disease

Diagnosis

Diagnosing Caroli disease typically involves imaging studies and clinical history. Diagnostic tools include:

• Ultrasound: May show cystic dilatation of intrahepatic bile ducts

• CT scan or MRI: Particularly MRCP (Magnetic Resonance Cholangiopancreatography), which provides detailed visualization of the bile ducts and is the imaging modality of choice

• ERCP (Endoscopic Retrograde Cholangiopancreatography): Can be used for diagnosis and therapeutic intervention

• Liver biopsy: May be necessary to evaluate the degree of fibrosis or confirm Caroli syndrome

• Genetic testing: Can identify PKHD1 mutations in syndromic cases

• Blood tests: May show elevated liver enzymes or markers of infection during cholangitis

Treatment

Treatment of Caroli disease focuses on managing symptoms, treating complications, and preventing long-term damage. Options include:

• Antibiotics: For managing episodes of cholangitis

• Ursodeoxycholic acid: To improve bile flow and reduce stone formation

• Endoscopic therapy: ERCP may be used to remove bile duct stones or relieve obstruction

• Surgical resection: If the disease is localized to one part of the liver, segmental hepatectomy can be curative

• Liver transplantation: May be required in severe, diffuse disease or in cases with liver failure or recurrent infections

• Management of portal hypertension: In cases of Caroli syndrome, with medications or surgical shunts as needed

Prognosis

The prognosis of Caroli disease depends on the extent of liver involvement and the presence of complications. Patients with localized disease may have a favorable outcome after surgical resection. However, those with diffuse disease, recurrent cholangitis, or associated hepatic fibrosis may experience progressive liver damage. There is also an increased lifetime risk of developing cholangiocarcinoma. Early diagnosis, careful monitoring, and appropriate management of infections and biliary complications are essential for improving outcomes and quality of life.