Caroli Disease – A Comprehensive Review

Introduction

Caroli Disease is an uncommon congenital disorder affecting the intrahepatic bile ducts, characterised primarily by segmental, non-obstructive saccular or fusiform dilatation. Despite its rarity, the disease presents significant diagnostic and therapeutic challenges and is associated with considerable morbidity due to complications such as recurrent bacterial cholangitis, stone formation, and risk of malignant transformation.

Definition and Classification

Description

Caroli Disease is a congenital disorder of the intrahepatic bile ducts, first described by Jacques Caroli in 1958. The hallmark of the disease is the segmental, multifocal, non-obstructive dilatation of the larger intrahepatic bile ducts. The condition is distinct from other cystic diseases of the liver due to its unique radiological and pathological features. The dilatations may be saccular or fusiform and are typically distributed in a segmental manner, often involving one or more hepatic lobes.

Types: Simple Caroli Disease vs. Caroli Syndrome

Caroli Disease is classified into two major forms:

• Simple Caroli Disease: This form involves only the bile duct dilatation without associated hepatic fibrosis or renal abnormalities.
• Caroli Syndrome: This variant combines the bile duct dilatation with congenital hepatic fibrosis and is frequently associated with polycystic kidney disease. Caroli Syndrome is considered to have a worse prognosis due to the added complications from hepatic fibrosis and renal involvement.

The distinction is clinically significant, as the presence of hepatic fibrosis and renal anomalies influences the disease course, management, and outcomes.

Epidemiology

Prevalence

Caroli Disease is rare, with an estimated incidence ranging from 1 in 1,000,000 to 1 in 100,000 live births. The true prevalence may be underestimated due to misdiagnosis or underreporting, especially in resource-limited settings.

Demographics

Both males and females may be affected, with no significant gender predilection. The disease commonly presents in childhood or early adulthood, although cases have been reported across all age groups. Caroli Syndrome tends to manifest earlier due to the associated hepatic and renal complications.

Geographic Distribution

Caroli Disease has been reported worldwide, with no clear geographic predilection. However, higher rates of diagnosis may occur in regions with advanced imaging capabilities and awareness of congenital hepatobiliary diseases. Some studies suggest a possible increase in cases among populations with high rates of consanguinity, reflecting the genetic basis of the disease.

Etiology and Pathogenesis

Genetic Factors

Caroli Disease is considered a congenital malformation and is most commonly inherited in an autosomal recessive manner. Mutations in the PKHD1 gene, which encodes the protein fibrocystin/polyductin, have been implicated, especially in cases associated with Caroli Syndrome and polycystic kidney disease. The genetic basis explains the frequent familial clustering and association with other ductal plate malformations.

Molecular Mechanisms

The pathogenesis involves abnormal remodelling of the ductal plate during embryogenesis. The ductal plate is a cylindrical layer of biliary precursor cells surrounding the portal vein branches, which normally remodel to form mature intrahepatic bile ducts. In Caroli Disease, this remodelling is incomplete, resulting in persistent, cystically dilated bile ducts. The defective fibrocystin/polyductin disrupts cellular signalling, leading to altered cell proliferation and bile duct morphogenesis.

Associated Conditions

Caroli Syndrome is frequently associated with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease (ARPKD). Other ductal plate malformations, such as congenital hepatic fibrosis and choledochal cysts, may co-exist. The presence of renal involvement is an important prognostic factor and influences management decisions.

Pathophysiology

The primary pathological feature of Caroli Disease is the segmental, non-obstructive dilatation of the intrahepatic bile ducts. Stasis within these dilated ducts promotes the formation of intrahepatic biliary stones (hepatolithiasis) and predisposes to recurrent bacterial cholangitis. Chronic inflammation may lead to secondary biliary cirrhosis, portal hypertension, and, in the case of Caroli Syndrome, progressive hepatic fibrosis. The abnormal bile ducts also increase the risk for cholangiocarcinoma, particularly in long-standing cases.

Clinical Presentation

Signs and Symptoms

The clinical manifestations of Caroli Disease are variable, ranging from asymptomatic cases discovered incidentally to severe, life-threatening complications. Common presenting features include:

• Recurrent abdominal pain: Often due to biliary obstruction or cholangitis.
• Fever and jaundice: Indicative of acute cholangitis.
• Pruritus: Related to cholestasis.
• Hepatomegaly: Frequently palpable on examination.
• Portal hypertension: Manifesting as splenomegaly, ascites, and variceal bleeding, especially in Caroli Syndrome.
• Complications: Hepatolithiasis, sepsis, hepatic abscesses, and, rarely, cholangiocarcinoma.

Complications

The complications of Caroli Disease are primarily related to bile stasis and infection:

• Recurrent bacterial cholangitis: Due to stagnant bile within dilated ducts.
• Intrahepatic biliary stones (hepatolithiasis): Formed as a result of prolonged stasis.
• Secondary biliary cirrhosis: From chronic inflammation and fibrosis.
• Portal hypertension: Particularly in Caroli Syndrome.
• Cholangiocarcinoma: Increased risk, especially with longstanding disease.
• Renal impairment: In cases with associated polycystic kidney disease.

Diagnosis

Imaging Modalities

Radiological imaging is central to the diagnosis of Caroli Disease. Key modalities include:

• Ultrasonography: May reveal cystic dilatations of the intrahepatic bile ducts, but specificity is limited.
• Computed Tomography (CT): Demonstrates saccular or fusiform dilatations; may show the characteristic “central dot sign,” representing portal vein radicles within the dilated ducts.
• Magnetic Resonance Cholangiopancreatography (MRCP): Provides detailed images of the biliary tree and is the investigation of choice. The “central dot sign” is best visualised on MRCP.
• Endoscopic Retrograde Cholangiopancreatography (ERCP): Used selectively for both diagnostic and therapeutic purposes.

Laboratory Investigations

Laboratory findings are typically non-specific but may include:

• Elevated liver enzymes: Suggests cholestasis or hepatic injury.
• Raised bilirubin levels: Indicative of obstructive jaundice.
• Leukocytosis: May be present during episodes of cholangitis.
• Renal function tests: Necessary in cases with suspected renal involvement.

Differential Diagnosis

Caroli Disease must be differentiated from other cystic and cholestatic liver diseases, such as:

• Choledochal cysts
• Primary sclerosing cholangitis
• Polycystic liver disease
• Cystic tumours of the liver
• Congenital hepatic fibrosis

Accurate differentiation is essential for appropriate management and prognostication.

Management and Treatment

Medical Therapy

The cornerstone of medical management is the treatment and prevention of complications:

• Antibiotics: For acute cholangitis and prophylaxis in recurrent cases.
• Ursodeoxycholic acid: May help reduce bile stasis and stone formation.
• Symptomatic management: Analgesics, antipyretics, and supportive care during acute episodes.

Surgical Options

Surgical intervention is indicated for localised disease, refractory symptoms, or complications:

• Resection of affected liver segments: Segmental hepatectomy may be curative in localised disease.
• Hepaticojejunostomy: For biliary drainage in selected cases.
• Liver transplantation: Reserved for diffuse disease, progressive hepatic failure, or intractable complications (e.g., recurrent cholangitis, cholangiocarcinoma).

The choice of therapy depends on the extent of disease, presence of hepatic fibrosis, and associated renal pathology.

Supportive Care

Supportive measures include nutritional optimisation, management of portal hypertension, and surveillance for complications such as cholangiocarcinoma. In Caroli Syndrome, renal function must be closely monitored, and nephrological interventions may be required.

Prognosis and Outcomes

The prognosis of Caroli Disease varies according to the form and severity of the disease, extent of hepatic involvement, and presence of complications. Patients with simple Caroli Disease and localised segmental involvement have a relatively good prognosis if treated appropriately. In contrast, Caroli Syndrome often leads to progressive hepatic and renal dysfunction, portal hypertension, and increased risk for cholangiocarcinoma.

Survival rates depend on early diagnosis, effective management of complications, and timely surgical intervention. Chronic infection, recurrent cholangitis, and malignant transformation are principal determinants of long-term outcomes. Liver transplantation offers excellent survival prospects in selected patients with advanced disease.

Nursing Care of Patients with Caroli Disease

Nursing care for these patients requires a multidisciplinary approach focusing on symptom management, complication prevention, patient education, and psychosocial support.

Assessment and Monitoring

Nursing assessment is crucial for early detection of complications and for guiding care plans.

Initial Assessment

• Obtain a thorough history: Note the frequency of abdominal pain, fevers, history of jaundice, and previous infections.
• Physical examination: Assess for liver size, tenderness, and signs of jaundice or pruritus.
• Monitor vital signs, especially temperature and heart rate, as fever and tachycardia may indicate infection.

Ongoing Monitoring

• Monitor for signs of cholangitis: chills, fever, right upper quadrant pain, and worsening jaundice.
• Observe for signs of hepatic decompensation: ascites, peripheral edema, confusion (hepatic encephalopathy), and gastrointestinal bleeding (due to varices).
• Evaluate laboratory results: liver function tests, white blood cell count, blood cultures if infection suspected, and coagulation profile.
• Monitor intake and output, as dehydration and electrolyte imbalances may occur during acute episodes.

Symptom Management

Pain Control

• Administer prescribed analgesics as needed, balancing adequate pain relief with the need to avoid hepatic toxicity (e.g., use paracetamol cautiously).
• Encourage non-pharmacological pain relief methods: positioning, relaxation techniques, and warm compresses.

Fever and Infection

• Monitor body temperature frequently.
• Administer antibiotics as prescribed, ensuring timely dosing to combat infections efficiently.
• Monitor for sepsis: hypotension, tachycardia, confusion, and decreased urine output.
• Encourage oral fluids if not contraindicated and maintain adequate hydration.

Jaundice and Pruritus

• Monitor skin color, sclera, and urine color to assess progression of jaundice.
• For pruritus, use emollients and keep the skin moisturized. Antihistamines may be prescribed to reduce itching.
• Encourage regular bathing with lukewarm water and mild soap to prevent skin breakdown.

Nutritional Support

• Assess nutritional status regularly, as malnutrition is common in chronic liver disease.
• Encourage a balanced, high-calorie, high-protein diet, as tolerated.
• Coordinate with a dietitian for individualized dietary plans, especially if there is evidence of hepatic encephalopathy (where protein intake may need restriction).
• Monitor for signs of fat-soluble vitamin deficiencies (A, D, E, K) due to bile flow impairment.

Fluid and Electrolyte Balance

• Monitor for ascites and edema; daily weight measurement and abdominal girth assessment are essential.
• Strictly monitor intake and output; note changes that may indicate fluid overload or deficit.
• Electrolytes should be checked routinely, and abnormalities corrected as ordered.

Prevention of Complications

Biliary Stone Formation

• Monitor for signs of biliary obstruction: worsening jaundice, dark urine, pale stools, and intense pruritus.
• Prepare for possible interventional radiology or surgical procedures to remove stones or relieve obstruction.

Portal Hypertension and Variceal Bleeding

• Watch for signs of gastrointestinal bleeding: hematemesis, melena, or sudden drop in blood pressure.
• Educate on avoiding NSAIDs and other medications that increase bleeding risk.
• Ensure access to emergency interventions for variceal bleeding (e.g., endoscopic band ligation).

Hepatic Encephalopathy

• Monitor mental status changes: confusion, drowsiness, personality changes.
• Administer lactulose and other medications as prescribed to reduce ammonia levels.
• Educate family and caregivers on early warning signs.

Patient Education and Support

Understanding the Disease

• Provide information about Caroli disease, its symptoms, potential complications, and the importance of adherence to treatment.
• Use educational materials appropriate to the patient’s learning level and language.

Medication Adherence

• Teach the importance of completing antibiotics and all prescribed medications.
• Review potential side effects and what to do if they occur.

Recognizing Warning Signs

• Educate patients and families on symptoms that require immediate medical attention: high fever, severe abdominal pain, confusion, vomiting blood, or black tarry stools.
• Provide emergency contact information and clear instructions on when and how to seek help.

Lifestyle Modifications

• Encourage avoidance of alcohol and hepatotoxic drugs.
• Stress the importance of routine follow-up with hepatology and gastroenterology specialists.
• Discuss the benefits of vaccinations (hepatitis A and B, and pneumococcal vaccine) to prevent secondary infections.

Psychosocial Support

• Assess for anxiety and depression, which may occur due to chronic illness and frequent hospitalizations.
• Provide emotional support and counseling resources as needed.
• Encourage participation in patient support groups or connecting with others who have chronic liver conditions.

Collaborative Care and Multidisciplinary Approach

Caring for a patient with Caroli disease involves a team approach:

• Physicians (hepatologists, gastroenterologists, surgeons) for diagnosis and advanced management
• Dietitians for nutritional planning
• Pharmacists for medication management and education
• Social workers and psychologists for counseling and support
• Nurses as coordinators and advocates for patient-centered care

Special Considerations

Pediatric Patients

• Pediatric cases may present with more severe symptoms or associated congenital abnormalities.
• Care must be tailored to developmental needs and involve family-centered education.

Surgical and Interventional Procedures

• Prepare patients and families for possible procedures such as biliary drainage, stone removal, or even liver transplantation in severe cases.
• Provide pre- and post-operative care, including monitoring for infection, bleeding, and pain management.

REFERENCES

1. National Organization for Rare Disorders (U.S.). Caroli Disease. https://rarediseases.org/rare-diseases/caroli-disease/. Last updated 8/10/2020.
2. Shi W, Yang AM. Caroli disease: an update on pathogenesis. https://pubmed.ncbi.nlm.nih.gov/34711722/. Chin Med J (Engl). 2021 Oct 26;134(23):2844-2846.
3. Umar J, Kudaravalli P, John S. Caroli Disease. https://www.ncbi.nlm.nih.gov/books/NBK513307/. 2023 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.
4. Shi W, Yang AM. Caroli disease: an update on pathogenesis. Chin Med J (Engl). 2021 Oct 26;134(23):2844-2846.
5. Fahrner R, Dennler SG, Inderbitzin D. Risk of malignancy in Caroli disease and syndrome: A systematic review. World J Gastroenterol. 2020 Aug 21;26(31):4718-4728.
6. Kyalwazi B, Kudaravalli P, John S. Caroli Disease. [Updated 2024 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513307/
7. Kyalwazi B, Kudaravalli P, John S. Caroli Disease. 2024 Aug 16. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30020679.

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