What are the presentation, diagnostic work‑up, and treatment options for Caroli disease?

Caroli Disease: Clinical Overview

Definition and Classification

Caroli disease is a rare congenital disorder characterized by segmental saccular or fusiform dilatation of the intrahepatic bile ducts (Type V choledochal cysts in the Todani classification), and must be distinguished from Caroli syndrome, which additionally features congenital hepatic fibrosis and renal cystic disease. 1

The key histological distinction is the presence or absence of hepatic fibrosis:

• Caroli disease: Isolated intrahepatic bile duct dilatation without fibrosis 1
• Caroli syndrome: Bile duct dilatation plus congenital hepatic fibrosis, likely part of the autosomal recessive polycystic kidney disease (ARPKD) spectrum 1

Clinical Presentation

Patients typically present during childhood or early adulthood with recurrent cholangitis as the dominant feature 2, 3:

• Recurrent cholangitis (most common): fever, right upper quadrant pain, jaundice 3, 4
• Intrahepatic stones (hepatolithiasis) complicating the dilated ducts 2, 4
• Hepatic abscess formation from recurrent infections 2

In Caroli syndrome specifically, portal hypertension manifestations dominate: esophageal varices, splenomegaly, and portosystemic shunting due to congenital hepatic fibrosis 1. Renal cystic lesions are present in the majority of Caroli syndrome patients, though severity of renal and hepatic manifestations do not correlate 1

Diagnostic Work-Up

Imaging Algorithm

Magnetic resonance cholangiopancreatography (MRCP) is the diagnostic modality of choice, providing optimal visualization of the biliary tree and demonstrating continuity between cystic lesions and bile ducts. 1, 3, 4

The diagnostic imaging approach should proceed as follows:

1. MRCP with contrast-enhanced MRI sequences: Demonstrates segmental intrahepatic saccular or fusiform cystic areas, shows the pathognomonic "central dot sign" (fibrovascular bundles within dilated ducts), and confirms communication with the biliary tree 1

2. CT with contrast may be used as an alternative but is less accurate than MRI/MRCP for biliary tree visualization 1

3. Ultrasound can identify cystic lesions but has limitations in fully characterizing the disease 1

Avoid endoscopic retrograde cholangiopancreatography (ERCP) for diagnostic purposes due to increased risk of biliary infection in these patients. 1

Additional Assessments

• Non-invasive liver stiffness measurements to assess degree of hepatic fibrosis, particularly important for distinguishing Caroli syndrome from Caroli disease 1
• Renal imaging (ultrasound, CT, or MRI) to identify renal cystic lesions suggestive of Caroli syndrome 1
• Genetic testing for PKHD1 mutations has little role in routine clinical practice due to the gene's size, complex splicing, and difficulty interpreting functional consequences 1

Treatment Options

Localized Disease (Monolobar Involvement)

For disease confined to one hepatic lobe, hepatic resection is the definitive treatment, relieving symptoms and eliminating malignancy risk in the resected segment. 2, 5

• Surgical resection offers acceptable morbidity (16%) and virtually no mortality 5
• Removes the affected lobe and associated cholangiocarcinoma risk 2, 5
• Provides long-term symptom relief with no recurrence in the resected territory 5

Diffuse Disease (Bilobar Involvement)

Orthotopic liver transplantation is the only effective definitive treatment for diffuse Caroli disease or syndrome. 3, 4, 6

Conservative management options for patients awaiting transplantation or who are not transplant candidates:

• Antibiotics for cholangitis episodes: Third-generation cephalosporins, fluoroquinolones, ureidopenicillins, or carbapenems for 4-6 weeks 7
• Ursodeoxycholic acid for hepatolithiasis management 3
• Endoscopic or percutaneous drainage procedures for symptomatic biliary obstruction or stone extraction 2, 4

Management of Caroli Syndrome-Specific Complications

• Portal hypertension management: Beta-blockers for variceal prophylaxis, endoscopic variceal ligation as needed 1
• Monitor renal function given frequent renal involvement 1

Surveillance for Cholangiocarcinoma

All patients with Caroli disease or syndrome should undergo annual surveillance with MRCP for cholangiocarcinoma detection starting at diagnosis. 1

The rationale for aggressive surveillance:

• Cholangiocarcinoma prevalence is 7% in Caroli disease/syndrome, dramatically higher than the general population (0.05%) 1, 2
• Chronic inflammation from recurrent cholangitis, biliary stasis, and gallstone irritation contribute to carcinogenesis 1
• Pre-operative detection is difficult due to abnormal biliary anatomy 1

CA19-9 testing has poor diagnostic properties for cholangiocarcinoma screening and is not recommended. 1 Definitive diagnosis requires pathological examination of affected tissues 1

Critical Surveillance Caveat

Cholangiocarcinoma recurrence rates up to 75% have been reported after liver resection or transplantation in Caroli patients, though this likely overestimates true recurrence given low overall cholangiocarcinoma rates in these studies 1

Key Clinical Pitfalls

• Do not delay diagnosis: Consider Caroli disease in any patient with chronic cholestasis of unknown cause or recurrent cholangitis 4
• Do not use ERCP diagnostically: The increased infection risk outweighs diagnostic benefits when MRCP is available 1
• Do not underestimate malignancy risk: The 7% cholangiocarcinoma prevalence mandates lifelong surveillance 1
• Distinguish Caroli disease from syndrome: The presence of congenital hepatic fibrosis fundamentally changes prognosis and management priorities toward portal hypertension complications 1