Caroli’s Disease: Causes, Symptoms, and Treatment

Caroli’s disease is a rare congenital hepatobiliary disorder that specifically affects the structure of the intrahepatic bile ducts. It is characterized by segmental dilatation of these bile ducts, a phenomenon that leads to bile stasis and the occurrence of complications such as repeated infections, gallstone formation, or progressive liver damage.

Although it is a congenital disease, clinical manifestations can appear at any age, often being mistaken for other liver conditions. Caroli’s disease includes several forms of presentation, the most complex being Caroli’s syndrome, which also associates congenital hepatic fibrosis.

Below, you will discover what causes Caroli’s disease, how it manifests, how it can be correctly diagnosed, and what treatment options are available to reduce the impact of this pathology on patients’ quality of life.

What is Caroli’s disease and how does it manifest in the bile ducts?

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Caroli’s disease is a rare, genetically derived liver condition characterized by congenital dilatation of the intrahepatic bile ducts. The dilatations can be saccular or fusiform and may abnormally connect with the main bile duct system, affecting the normal transport of bile from the liver to the intestine.

Bile stasis in the dilated ducts promotes the formation of gallstones and predisposes to recurrent bile duct infections, such as cholangitis. Recurrent infections can lead to liver tissue degradation, fibrosis, and, in advanced cases, the development of biliary cirrhosis. The dilatations that occur are not caused by a mechanical obstruction, which distinguishes it from other biliary conditions like gallstones or bile duct tumors.

Severe forms of the disease can be associated with congenital anomalies such as hepatic fibrosis or polycystic kidney disease. This association is called Caroli’s syndrome and negatively impacts the overall prognosis, requiring a multidisciplinary medical approach.

Symptoms vary from patient to patient. Frequent manifestations include abdominal pain in the right upper quadrant, recurrent episodes of fever and chills, jaundice, and hepatomegaly. Sometimes, the diagnosis is made incidentally following imaging investigations performed for other reasons.

A major risk in the disease’s progression is the occurrence of cholangiocarcinoma, an aggressive form of bile duct cancer. The estimated risk is about 100 times higher compared to the general population, which justifies careful monitoring and periodic evaluation of patients diagnosed with Caroli’s disease.

In the context of a liver affected by structural and functional changes, it is essential to support liver health through complementary means. A formula like Premium Hepato-Care Formula, which contains 7 ingredients with proven benefits for the liver—including milk thistle, artichoke, turmeric, and L-Glutathione—can contribute to protecting, detoxifying, and regenerating liver cells. Daily use of this supplement can provide valuable support in maintaining optimal liver function and preventing progression to severe liver complications.

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Causes of Caroli’s disease and risk factors involved

Caroli’s disease, as well as Caroli’s syndrome, are rare genetic diseases resulting from mutations in the PKHD1 gene. The gene is responsible for the synthesis of a protein involved in the normal development of bile ducts and renal tubules. Damage to the gene causes structural changes in the intrahepatic bile duct system and kidneys.

The disease is typically transmitted in an autosomal recessive manner, meaning that two copies of the mutated gene – one from each parent – are required for the disease to manifest. Carriers of a single copy do not show symptoms but can pass the mutation to their offspring.

In some cases, the mutation occurs spontaneously, without a prior family history, which can make it difficult to anticipate the genetic risk within the family.

The disease is frequently associated with other congenital hepatic and renal malformations, such as congenital hepatic fibrosis and polycystic kidney disease. This association indicates common genetic mechanisms affecting both organs.

Main symptoms and signs of Caroli’s disease

Caroli’s disease manifests through the appearance of dilatations of the intrahepatic bile ducts, which promote bile stasis and stone formation. The presence of stones causes partial or total obstruction of bile flow, which results in local inflammation, known as cholangitis. The symptoms experienced by the patient are primarily caused by these complications.

Manifestations occur in episodes, and each episode is accompanied by classic symptoms. The most frequent ones are:

• pain in the upper right abdomen;
• vomiting;
• fever;
• jaundice (yellowish discoloration of the skin and sclera).

Some patients may have frequent episodes of cholangitis, while others may experience only a single episode throughout their lives. In rarer cases, bile duct dilatation can lead to the development of bile duct tumors, with symptoms that may vary depending on the location and extent of the lesion.

Symptoms generally appear before the age of 30, but there is no fixed limit for clinical onset.

Diagnosis of Caroli’s disease and necessary investigations

Diagnosing Caroli’s disease is challenging because the symptoms are nonspecific and are also found in other hepatobiliary conditions. Jaundice, fever, and right upper quadrant pain can be present in several diseases, which is why it is essential to rule out other causes before establishing the correct diagnosis. Choledochal cysts, bile duct tumors, cholangiocarcinoma, infectious cholangitis, or primary sclerosing cholangitis can have similar manifestations. All of these must be considered in the differential diagnosis.

Clinical suspicion arises based on symptoms and the patient’s history. The gastroenterologist, along with the geneticist, decides on the necessary investigations:

• Abdominal ultrasound is often the first step, followed by imaging examinations such as computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP), which visualize the bile duct system. MRCP allows for precise identification of bile duct dilatations, stones, and potential stenoses.
• ERCP, once considered the diagnostic standard, is now primarily used therapeutically due to associated risks. Percutaneous cholangiography is sometimes indicated in selected cases.
• Blood tests include liver and kidney function tests, and inflammatory markers. In selected cases, genetic testing is recommended to identify the PKHD1 mutation.

Overall, combining imaging, biological, and genetic results allows for confirmation of the diagnosis and exclusion of other conditions with similar presentations.

Treatment of bile duct dilatations and hepatic bile cysts in the context of Caroli’s disease

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Treatment for Caroli’s disease is determined by the degree of bile duct involvement and the location of the dilatations within the liver. In situations where the dilatations are confined to a single liver lobe, surgical resection of the affected part (segmental, left, or right hepatectomy) may be performed. Generally, the results are favorable, with a low risk of symptom recurrence.

When the dilatations are distributed diffusely throughout the liver parenchyma, radical surgical treatment is not indicated. In such cases, conservative treatment is chosen, which may include antibiotics, bile drainage (percutaneous or surgical), and periodic clinical follow-up. In advanced forms, liver transplantation becomes a therapeutic option, especially in the presence of severe complications or associated diseases.

Therefore, the decision regarding the type of treatment is made by a multidisciplinary medical team, consisting of a gastroenterologist, a hepatobiliary surgeon, and, if necessary, a liver transplant specialist. The choice of the appropriate intervention depends on the anatomical and clinical specificities of each case.

Possible complications of Caroli’s disease

Caroli’s disease can lead, in its progression, to severe complications, with a major impact on liver function and the patient’s general condition:

● Recurrent biliary infections (cholangitis)

Bile duct dilatation favors bile stasis and stone formation, leading to frequent infection episodes. Each episode of cholangitis worsens the progression of liver disease.

● Intrahepatic biliary lithiasis

Bile precipitates formed in the dilated ducts lead to chronic obstruction and persistent inflammation, increasing the risk of severe complications such as abscesses.

● Liver abscesses

Untreated or incompletely treated cholangitis can progress to the formation of liver abscesses, with the potential for systemic dissemination.

● Portal hypertension and biliary cirrhosis

Chronic inflammation and liver fibrosis lead to increased pressure in the portal system, with the appearance of esophageal varices and ascites. In the final stages, the disease can progress to biliary cirrhosis.

● Cholangiocarcinoma

Patients with Caroli’s disease have up to 100 times higher risk of developing bile duct cancer compared to the general population. This is one of the most serious complications, with a poor prognosis.

● Liver failure

Progressive destruction of the liver parenchyma and loss of excretory function lead to liver decompensation, sometimes requiring transplantation.

● Renal complications

In Caroli’s syndrome, damage to the renal tubules leads to the formation of multiple cysts, with a risk of chronic kidney failure.

In conclusion, Caroli’s disease is a rare genetic condition characterized by dilatation of the intrahepatic bile ducts. As the symptoms are similar to those of other hepatobiliary diseases, it is important that the diagnosis is based on specific imaging investigations and, when necessary, genetic tests. Depending on the location of the dilatations, treatment can vary: if the involvement is limited, surgical intervention is recommended; if it is extensive, a conservative approach or liver transplantation is preferred.

Therefore, establishing the correct diagnosis, choosing the appropriate treatment, and constant monitoring are essential for preventing complications and improving patients’ quality of life.

References:

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4. Wang ZX, Li YG, Wang RL, et al. Clinical classification of Caroli’s disease: an analysis of 30 patients. HPB (Oxford). 2015;17(3):278-283;

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