What is Caroli Disease?
Caroli disease, also known as congenital communicating cavernous ectasia of the biliary tree, is a rare inherited condition that affects the large ducts within the liver, causing them to widen abnormally. This disease can be found throughout the liver or just in certain areas, and may form a sack that creates cyst-like structures that communicate with the bile-passing branches in the liver. Usually, the condition is diagnosed during the teenage years and is noted by recurrent episodes of cholangitis, which is an infection in the bile tubes, and lacks scarring around the portal area in the liver.
While most people with Caroli disease don’t have a family history of it, there have been some cases where it is inherited in a dominant manner from one parent, and may have an association with an inherited kidney disease called autosomal dominant polycystic kidney disease. There is another version of the illness called Caroli syndrome, which is characterized by the same biliary tract malformations as classic Caroli disease, but also includes a condition known as congenital hepatic fibrosis, which causes scarring of the liver. Caroli syndrome is inherited from both parents in a recessive manner, and is associated with a different inherited kidney disease, called autosomal recessive polycystic kidney disease (ARPKD).
Treatment for both of these conditions is generally supportive and includes antibiotics, and if necessary, a procedure called endoscopic retrograde cholangiopancreatography (ERCP). This procedure is used to treat blockages or backups in the bile tubes.
What Causes Caroli Disease?
Caroli disease is a condition named after Dr. Jacques Caroli, a French doctor who first identified it in 1958. He described the disease as abnormal swelling in the bile ducts within the liver, without any blockages.
This disease is caused by a genetic disorder involving the PKHD1 gene, which impacts a protein called fibrocystin. This protein is found in several parts of the body including kidney cells, liver cells, and the pancreas. Any genetic issues with this protein can cause changes in the kidney and liver that are similar to tiny fibrous cysts.
Caroli disease is often found in people who also have a kidney disease that is passed down through families, known as autosomal recessive polycystic kidney disease (ARPKD).
Risk Factors and Frequency for Caroli Disease
This condition is quite rare, so exact data on its incidence and prevalence is not available. However, it is estimated to affect about 1 in every 10,000 newborns. It impacts both males and females equally, and is more commonly seen in people who are of Asian descent. The condition typically starts showing up in early adulthood, with more than 80% of patients being diagnosed before they reach 30 years of age.
Signs and Symptoms of Caroli Disease
Caroli disease is a condition that involves the liver and kidneys, leading to specific health issues. Usually, the kidneys are targeted first, with newborn babies often exhibiting polycystic kidneys. Eventually, liver abnormalities can develop later in life due to a discrepancy in the expression of the impacted fibrocystin gene. This is generally lower in the cells of bile ducts than in the cells of kidney tubes.
In those with Caroli disease, certain issues in the bile ducts can cause a buildup and blockage of bile. So, generally, patients might deal with recurring bacterial infections in their bile ducts. Symptoms of these infections might include abdominal pain, fever, chills, and a yellowing of the skin and eyes known as jaundice. Itching is also a common symptom, resulting from a build-up of bilirubin due to bile flow issues in the liver. Sometimes, Caroli disease can develop complications like liver scarring, leading to liver-related issues such as fluid accumulation in the abdomen and bleeding from swollen veins in the esophagus and stomach. It’s crucial to note that there’s an increased cancer risk, specifically cholangiocarcinoma or bile duct cancer, in patients with Caroli disease.
During a physical exam, doctors might notice tenderness in the upper right area of the abdomen, significant liver enlargement due to the disease, and yellowing of the whites of the patient’s eyes. If liver scarring has occurred, a phenomenon known as shifting dullness and fluid thrill might be noteworthy, indicating fluid buildup in the abdomen. Other signs of advanced liver damage, like spider-like blood vessels, can also be seen.
Testing for Caroli Disease
In simple terms, the laboratory work will identify if there are too many of a particular type of white blood cells, known as leukocytes, in your blood. High levels of leukocytes can indicate an infection or inflammation in the body. Blood tests can also identify if there are abnormal levels of a certain substance, called alkaline phosphatase, and a yellow substance, called bilirubin. If these are elevated, it suggests there could be inflammation in the bile ducts, a condition known as cholangitis. The liver’s function to produce proteins and other important substances is usually unaffected.
The same signs of illness can be identified using different types of body scans. The first scan is usually an ultrasound, which shows if there are sac-like extensions (sacular dilatations) of the ducts inside the liver that carry bile (a digestive fluid).
A CT scan of your abdomen also shows if your liver is abnormally shaped and if there are gross dilatations — significant stretches or enlargements of your internal structures. It may also show a specific sign, called the ‘central dot sign,’ which looks like a dark fluid-filled enlargement (cystic dilatation) around a bright central spot marking the portal tract. This tract is part of your liver’s blood supply system. You may also see the small ducts that carry bile within the liver (intrahepatic bile duct canaliculi).
Other scans that visualize the bile ducts, such as an endoscopic retrograde cholangiopancreatography (ERCP) or a magnetic retrograde cholangiopancreatography (MRCP), show if there’s a non-blocking cystic dilatation that communicates with the biliary tree. This tree is the system of ducts that carry bile from your liver to your small intestine. The advantage of ERCP is that it can also be used therapeutically to remove an impacted stone by using a procedure that cuts a small opening in the muscle surrounding the duct (sphincterotomy) and a sweeping action with a balloon.
A liver biopsy, a procedure where a small piece of liver tissue is removed and examined, is rarely done. When it is performed, it’s usually to look for signs of related liver scarring (hepatic fibrosis).
Treatment Options for Caroli Disease
When dealing with cholangitis, which is an inflammation of the bile duct system often caused by biliary obstruction, the main treatment involves supportive care that is tailored according to individual symptoms. Care often involves the use of antibiotics that fight against a certain type of bacteria known as gram-negative rods and anaerobic rods. Sometimes, doctors may need to ensure that bile is flowing freely from the liver to the small intestine. This can be achieved by placing a tiny tube known as a biliary stent within the bile duct. The stent can be placed either through a procedure known as endoscopic retrograde cholangiopancreatography (ERCP) or through a procedure guided by an interventional radiologist that involves placing a catheter into the liver (percutaneous trans-hepatic catheter or PTC). PTC is more effective for blockages within the liver and patients may need to have the catheter in place for a while, requiring periodic cleaning and changing.
For severe cholestasis, a condition where bile cannot flow from the liver to the duodenum, a medication known as ursodeoxycholic acid is used. For Caroli disease, a rare genetic disorder that can result in chronic liver disease, some doctors have recommended specific surgical procedures such as segmentectomy (removal of a portion of the liver), lobectomy (removal of a large portion of the liver) or hepaticojejunostomy (a surgical procedure that reroutes the flow of bile) depending upon the extent of the disease.
When liver scarring or fibrosis occurs, it can lead to an increase in pressure within the liver’s blood vessels, a condition known as portal hypertension. This can result in variceal bleeding (bleeding from enlarged veins) and recurrent ascites (accumulation of fluid in the abdominal cavity). These complications are managed similarly to when they occur due to liver cirrhosis, such as with medications called non-selective beta-blockers, banding procedures to prevent bleeding from enlarged veins (endoscopic band ligation), and diuretic therapy for ascites (medications that help the body get rid of excess fluid).
Liver transplantation is currently the only definitive treatment for Caroli syndrome, a serious form of Caroli disease. Indications for liver transplantation in Caroli syndrome include deterioration of liver function (hepatic decompensation), recurring cholangitis unresponsive to treatment, and the presence of a specific type of cancer (focal adenocarcinoma).
The timely surgical treatment is crucial because of the serious prognosis of cholangiocarcinoma, a cancer that arises from the cells within the bile ducts. Studies have demonstrated superior long-term outcomes with liver resection (removal of part of the liver) in unilobar Caroli disease or a liver transplant in diffuse Caroli disease complicated with cholangitis or portal hypertension.
What else can Caroli Disease be?
When an individual presents certain symptoms, doctors may suspect several different conditions before landing on the correct diagnosis. These conditions might include ascending cholangitis or acute cholecystitis.
When looking at medical scans, certain features may make the doctors consider a range of diseases. These include choledochal cysts (bile duct cysts), liver abscesses (pus-filled pockets in the liver), and primary sclerosing cholangitis (a disease that damages the liver’s bile ducts).
Type V choledochal cysts are a unique case in which the bile ducts inside the liver have stretched into a cyst-like shape. However, unlike Caroli disease, these cysts don’t have the same genetic abnormalities. Meanwhile, Todani classification groups Caroli disease with type V choledochal cysts because of their similarities.
What to expect with Caroli Disease
The outlook for someone with Caroli disease depends on how severe the genetic abnormality causing the disease is and how many different organs are affected. Caroli disease often leads to recurring blockages in the bile ducts and fibrosis, a condition where tissues become thickened and scarred. These can both make a person quite sick. Currently, the only definitive treatment is a liver transplant.
People with Caroli disease are also at a higher risk for cholangiocarcinoma, a type of cancer that starts in the bile ducts. This type of cancer often has a poor prognosis, meaning it can be difficult to treat and can potentially lead to serious health issues.
Possible Complications When Diagnosed with Caroli Disease
Potential complications of this condition can include recurring inflammation of the bile duct, stones inside the liver, abscesses, and the development of bile duct cancer.
Complications:
- Recurring inflammation of the bile duct
- Stones inside the liver
- Abscesses
- Development of bile duct cancer