Caroli Disease: Symptoms, Types, Causes and Treatment

Caroli disease is a rare and intriguing disorder that affects the liver’s bile ducts, leading to a variety of symptoms and serious complications. Although first described over half a century ago, the disease remains a diagnostic and therapeutic challenge due to its rarity, varied presentation, and risk of life-threatening complications. In this article, we’ll explore the symptoms, types, causes, and treatment options for Caroli disease, drawing on the latest clinical research and expert insights.

Symptoms of Caroli Disease

Caroli disease is often a masquerader, presenting with a broad spectrum of symptoms that can mimic other liver or biliary conditions. Recognizing the hallmark signs is essential for early diagnosis and effective management, as timely intervention can prevent complications such as infections, liver failure, or even cancer.

Symptom	Description	Frequency/Association	Source(s)
Cholangitis	Recurrent bacterial infection of bile ducts	Most common	1,2,3,4,5
Abdominal Pain	Right upper quadrant or epigastric pain	Frequent, often severe	3,5,10
Jaundice	Yellowing of skin and eyes	Associated with cholestasis	3,4,5
Fever	Often with cholangitis, sometimes recurrent	Common	4,5,10
Portal Hypertension	Enlarged spleen, varices, ascites	Especially in Caroli syndrome	1,4,7
Hematemesis/Melena	Vomiting blood/black stool (from varices)	In portal hypertension	4,7
Hepatomegaly/Splenomegaly	Enlarged liver/spleen	Portal hypertension/fibrosis	4,7
Pancreatitis	Inflammation of pancreas	Rare complication	5
Asymptomatic	No symptoms at diagnosis	Up to 1/3 of cases	6

Table 1: Key Symptoms

Understanding the Symptom Spectrum

Caroli disease can manifest at any age, but most patients present before age 30, though some are diagnosed much later 5,6,10. The most frequently reported symptom is recurrent cholangitis—infection of the bile ducts—characterized by fever, right upper abdominal pain, and jaundice 1,2,3,4,5. These episodes often recur and may become life-threatening if not managed promptly.

Cholangitis and Biliary Symptoms

• Cholangitis is the hallmark of Caroli disease, resulting from stagnant bile and bacterial infection in dilated intrahepatic ducts.
• Patients may also develop jaundice due to impaired bile flow.
• Right upper quadrant pain is common and may persist between infections.

Complications Related to Portal Hypertension

• In Caroli syndrome (a subtype), portal hypertension leads to splenomegaly, variceal bleeding (hematemesis, melena), and ascites 1,4,7.
• Hepatomegaly and splenomegaly are often detected during physical exam or imaging.

Other Presentations

• Pancreatitis is rare but can occur if stones or infection affect the pancreas 5.
• Some individuals may remain asymptomatic, with the disease discovered incidentally during imaging or evaluation for unrelated issues 6.
• Chronic abdominal pain or vague digestive symptoms may also be the presenting complaint, particularly in adults 10.

Types of Caroli Disease

Caroli disease is not a single entity but exists in distinct forms, each with specific clinical and pathological features. Understanding these types is crucial for diagnosis, prognostic evaluation, and treatment planning.

Type	Key Features	Associated Conditions	Source(s)
Type I (Simple)	Isolated bile duct dilatation	Recurrent cholangitis, stones	2,3,6,7
Type II (Caroli Syndrome)	Bile duct dilatation + hepatic fibrosis	Portal hypertension, cirrhosis, renal cysts	1,2,3,7,11

Table 2: Types of Caroli Disease

The Two Main Types Explained

Type I: Classic (Simple) Caroli Disease

• Features segmental, non-obstructive, saccular or fusiform dilatation of the intrahepatic bile ducts without hepatic fibrosis 2,3,7.
• Recurrent cholangitis and hepatolithiasis (intrahepatic stones) are typical 2,3.
• No portal hypertension or liver cirrhosis.
• Occurs in both children and adults; may be as common as the syndromic form 2,6.

Type II: Caroli Syndrome

• Combines bile duct dilatation with congenital hepatic fibrosis, leading to portal hypertension, varices, and progressive liver dysfunction 1,2,3,7.
• Renal cystic disease—especially autosomal recessive polycystic kidney disease (ARPKD)—is frequently associated 2,7,11.
• More likely to present in younger patients and those with symptoms of portal hypertension.
• Prognosis is poorer due to risk of liver failure and complications 1.

Other Notes on Classification

• Some literature refers to further subtypes based on anatomic extent (monolobar vs. diffuse) and clinical features, but the two main categories remain standard 6.
• Age of onset and blood test abnormalities (like anemia, leucopenia, and thrombocytopenia) may help differentiate types, with more cytopenias seen in Caroli syndrome due to portal hypertension 6.

Causes of Caroli Disease

The origins of Caroli disease are rooted in genetics and abnormal liver development, but environmental factors and associated conditions also play a role. Understanding the etiology helps inform prognosis, family counseling, and the search for associated disorders.

Cause/Factor	Mechanism/Details	Inheritance/Association	Source(s)
Genetic Mutation	PKHD1 gene mutations	Autosomal recessive	2,7,11,12
Ductal Plate Malformation	Abnormal fetal bile duct development	Fibrocystic liver & kidney diseases	11,12
Associated Renal Diseases	ARPKD, renal cysts	Common in Caroli syndrome	2,7,11,13
Choledochal Cyst	Abnormal bile duct cysts	Frequently coexists	2,5,9

Table 3: Causes and Associations

Genetic and Developmental Roots

Inheritance and Genetic Mutations

• Caroli disease is most often autosomal recessive in inheritance, requiring two copies of the abnormal gene 2,7,12.
• Pathogenic variants in the PKHD1 gene—also implicated in ARPKD—are a known cause, especially in Caroli syndrome 12.
• Family history may reveal other cases of liver or kidney cystic disease.

Ductal Plate Malformation

• During fetal development, the ductal plate (early bile duct structure) fails to remodel correctly, leading to segmental dilatation of the intrahepatic bile ducts 11.
• The extent and location of this abnormality determine whether a person develops classic Caroli disease, Caroli syndrome, or other related fibrocystic liver disorders.

Associated Disorders

• Renal cystic diseases, especially ARPKD, are commonly associated, reflecting the shared embryologic origin of bile ducts and kidney tubules 2,7,11.
• Choledochal cysts, or cystic dilations of the extrahepatic bile ducts, may coexist and contribute to symptoms or complications 2,5,9.
• Cholangiocarcinoma (bile duct cancer) develops in about 7% of cases, likely due to chronic inflammation and stasis within the abnormal ducts 2,8.

Treatment of Caroli Disease

Treating Caroli disease is highly individualized, depending on the type, extent of liver involvement, severity of symptoms, and presence of complications. A combination of medical, endoscopic, surgical, and sometimes transplant therapies is used to manage symptoms, prevent complications, and improve quality of life.

Treatment	Approach/Indication	Goals/Outcomes	Source(s)
Antibiotics	For acute/recurrent cholangitis	Control infection, prevent sepsis	1,3,5,11
Ursodeoxycholic Acid (UDCA)	Dissolves intrahepatic stones	Reduces cholestasis, stone burden	3,15
Endoscopic/Radiologic Drainage	Relieves biliary obstruction	Symptom relief, prevent infection	1,5,11,13
Hepatic Resection	Localized (monolobar) disease	Symptom cure, reduces cancer risk	2,3,10,14
Liver Transplantation	Diffuse or advanced disease, failure	Definitive cure, treats portal hypertension	1,3,11,13
Combined Hepato-Renal Transplant	Caroli syndrome with renal failure	Treats both liver and kidney disease	13

Table 4: Treatment Approaches

Medical and Supportive Therapy

Managing Cholangitis and Stone Disease

• Acute cholangitis is treated promptly with broad-spectrum antibiotics (often IV), to prevent sepsis and liver abscesses 1,3,5.
• Ursodeoxycholic acid (UDCA) can dissolve cholesterol-rich intrahepatic stones and promote bile flow; long-term use has led to remission and stone clearance in some cases 3,15.
• Supportive care includes analgesia, hydration, and nutritional support as needed.

Endoscopic and Radiologic Procedures

• Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous drainage are employed to relieve biliary obstruction or drain infected ducts/abscesses 1,5,11,13.
• These procedures are generally reserved for complications or as bridges to definitive therapy.

Surgical and Transplant Options

Hepatic Resection

• For monolobar (localized) disease, hepatectomy (removal of affected liver segment/lobe) can be curative, resolving symptoms and reducing malignancy risk 2,3,10,14.
• Surgical outcomes are generally favorable in selected patients.

Liver Transplantation

• For diffuse or severe Caroli disease, especially with Caroli syndrome or recurrent, intractable cholangitis and portal hypertension, liver transplantation is the treatment of choice 1,3,11,13.
• Transplantation offers the best chance of long-term survival and improved quality of life, with survival rates similar to other transplant indications 11,13.
• Patients with associated advanced renal disease (e.g., ARPKD) may require combined or sequential liver-kidney transplantation 13.

Surveillance & Follow-Up

• Regular monitoring for complications such as cholangiocarcinoma is vital, even after surgery or transplantation 8.
• Lifelong follow-up includes imaging, liver function tests, and symptom assessment.

Conclusion

Caroli disease, though rare, poses significant challenges due to its variable presentation, risk of life-threatening complications, and complex management. Early recognition, accurate differentiation of types, and individualized treatment are key to improving outcomes.

Key Takeaways:

• Caroli disease is characterized by segmental, non-obstructive dilatation of intrahepatic bile ducts and can present with recurrent cholangitis, abdominal pain, jaundice, and portal hypertension.
• There are two main types: classic Caroli disease (simple form) and Caroli syndrome (with congenital hepatic fibrosis and often renal involvement).
• The disease is autosomal recessive, caused by PKHD1 mutations and ductal plate malformation, frequently associated with renal cystic diseases and increased cancer risk.
• Treatment is tailored to disease type and severity, ranging from antibiotics and UDCA to surgery and liver transplantation for advanced or diffuse cases.
• Lifelong follow-up and surveillance for malignancy and complications are essential for all patients.

With ongoing advances in imaging, genetics, and transplantation, there is hope for better outcomes and quality of life for those affected by this complex disease.