Caroli Disease: Causes, Signs, Symptoms, Diagnosis, Complications, Treatment, Prevention and Prognosis

It is a rare genetic disorder that affects the bile ducts that carry bile from the liver to aid in the digestion of fats.

Researchers have identified two forms of Caroli’s disease.

Causes of Caroli’s disease

The complex form, which is also known as Caroli’s syndrome, is similarly characterized by widening of the bile ducts , but smaller bile duct malformations, congenital liver fibrosis (scarring of liver tissue), blood pressure discharge and kidney problems are also present.

The differences in the causes of the two forms have yet to be discovered.

The isolated form of Caroli’s disease is simply called Caroli’s disease, while the more severe form is known as Caroli’s syndrome.

The exact genetic mutation that causes Caroli’s disease and Caroli’s syndrome is not known. However, some people with Caroli’s syndrome may have a mutation in the PKHD1 gene .

It is found primarily in the kidneys, with lower levels in the liver, pancreas, and lungs.

The PKHD1 gene encodes a protein called fibrocystin, which is a receptor-like protein believed to be involved in tubulogenesis and maintenance of the bile duct.

A mutation in this gene is also believed to cause autosomal recessive polycystic kidney disease.

The simple form of Caroli’s disease is inherited, or passed between family members, as an autosomal dominant trait.

It can also occur in individuals with no family history of the disorder as a result of a spontaneous genetic mutation in the egg or sperm cells or in the developing embryo.

The complex form, Caroli’s syndrome, is inherited as an autosomal recessive trait.

Caroli’s syndrome is more common than Caroli’s disease, although the extent to which it is unclear.

Symptoms appear first in adults, although childhood and neonatal cases have been reported. There is no cure for Caroli’s syndrome or disease.

Treatment consists of controlling the symptoms. Mortality in Caroli’s disease is caused by complications.

After cholangitis (inflammation of the bile duct) occurs, which occurs in both disease and syndrome, a large number of patients die within 5 to 10 years.

Both of these conditions are more common in women than men.

Signs and symptoms of Caroli’s disease

General

Symptoms of Caroli’s disease and Caroli’s syndrome usually appear in adulthood, although symptoms have been reported in children and young babies.

Generally the first symptoms are: fever, intermittent abdominal pain and an enlarged liver, jaundice can even occur .

Congenital liver fibrosis

People with Caroli’s syndrome can experience congenital liver fibrosis, scarring of the liver tissue that can lead to portal hypertension , which occurs when the scar tissue blocks blood flow through the liver.

Pain

People with Caroli’s disease or Caroli’s syndrome may experience localized pain from cysts, which are closed sacs that may contain air, fluid, or semi-solid material that may disappear on their own or must be surgically removed.

People with any of the forms of the disease can develop cysts in the kidneys and enlarge the liver and spleen, and they can also have abdominal pain.

Portal hypertension

High blood pressure can develop in the portal vein, which carries blood from the digestive system to the liver, the most common cause of which is cirrhosis.

This scar tissue blocks the flow of blood through the liver. An enlarged liver or spleen can occur as a result of this condition.

Polycystic kidney disease

Although rare, polycystic kidney disease has occurred in people with Caroli’s syndrome. Polycystic kidney disease is associated with growths of numerous cysts in the kidneys.

These cysts can deeply enlarge the kidneys while replacing much of their normal structure, resulting in reduced kidney function and leading to kidney failure.

Enlargement of the bile ducts

Caroli’s disease and Caroli’s syndrome are associated with non-obstructive dilatation of the bile ducts.

This can cause recurrent bacterial cholangitis, which is a bacterial infection that occurs during bile duct inflammation.

Diagnosis of Caroli disease

The diagnosis is suspected on clinical grounds and confirmed by the detection of cystic dilatation in the biliary tree through imaging studies.

The key diagnostic procedure is magnetic resonance cholangiography which shows a characteristic appearance of abnormal bile ducts.

Differential diagnosis

Differential diagnosis should include primary sclerosing cholangitis, isolated polycystic liver disease, and hepatic cystic hamartoma, as well as hepatic and common bile duct cysts.

Prenatal diagnosis

Cases of prenatal diagnosis based on ultrasound findings have been reported.

Genetic counseling

Syndromic cases share an autosomal recessive transmission with congenital liver fibrosis and recessive polycystic kidney disease.

Biopsy

In a biopsy, a small sample of tissue is removed from the body and evaluated in a laboratory.

To help diagnose Caroli’s disease or Caroli’s syndrome, a liver biopsy may be done to determine the presence and extent of bile duct abnormalities.

The bile ducts carry bile from the liver to aid in the digestion of fats.

Also, the presence of cholangitis can be confirmed after examination of the tissue.

Imaging studies

Ultrasound, a non-invasive procedure that uses sound waves to create a moving image of internal organs, can be used to determine the extent of bile duct dilation.

MRI scans that use magnets to create an image of internal organs can be used to visualize the liver, kidneys, and bile ducts to examine the extent of inflammation and the presence of cysts.

Percutaneous transhepatic cholangiography is an x-ray test that can help show if there is an obstruction in the liver or the bile ducts that drain it.

Endoscopic retrograde cholangiopancreatography is an X-ray combined with an endoscope (a long, flexible lighted tube).

Through the endoscope, the doctor can see the stomach, duodenum, and ducts in the biliary tree and pancreas.

These techniques can help create a picture of the bile ducts and determine how inflamed they are.

While these techniques can be helpful, they are invasive and can cause complications.

Laboratory studies

Blood tests can reveal abnormal levels of white blood cells, which may indicate bacterial cholangitis, a bacterial infection that occurs during bile duct inflammation.

Laboratory tests can also be used to assess liver function, as evidenced by prothrombin, bilirubin, and albumin activity.

Caroli’s disease and Caroli’s syndrome can affect kidney function.

The blood urea nitrogen test is a test of kidney function and can be used in individuals with Caroli’s disease and Caroli’s syndrome to assess kidney function.

Urea is a by-product of protein metabolism. This waste product is formed in the liver, then filtered from the blood and excreted in the urine by the kidneys.

The blood urea nitrogen test measures the amount of nitrogen contained in urea.

High blood urea nitrogen levels may indicate kidney dysfunction.

But because blood urea is also affected by protein intake and liver function, the test is usually done in conjunction with a blood creatinine test, a more specific indicator of kidney function.

This test measures blood levels of creatinine, a byproduct of muscle energy metabolism that, like urea, is filtered from the blood through the kidneys and excreted in the urine.

With normal kidney function, the amount of creatinine in the blood remains relatively constant.

For this reason, and because creatinine is very little affected by liver function, elevated blood creatinine is a more sensitive indicator of kidney failure than elevated urea nitrogen.

Physical exam

A complete physical exam should check for an enlarged liver and spleen and tenderness in the upper right part of the abdomen.

Patient interview questions should look for a history of abdominal pain and a family history of kidney disease. Jaundice may be present.

Genetic testing

Deoxyribonucleic acid (DNA) tests may be available for Caroli syndrome, the complex and recessive form of the disorder, as it has been linked to a mutation in the PKHD1 gene.

This test cannot be definitive for the disease, as this gene has also been linked to autosomal recessive polycystic kidney disease.

Complications of Caroli’s disease

Bile duct cancer

People with Caroli’s syndrome, the complex form of the disorder, are about 100 times more likely than the general population to develop cholangiocarcinoma, the cancer of the bile ducts, which carries bile from the liver to aid in the digestion of fats.

Cholangiocarcinoma is considered an incurable and rapidly fatal disease.

Surgery is needed to remove the tumors. However, more often than not, the disease has progressed too far for surgery to be effective by the time it is discovered.

Bile duct infection

Cholangitis, a bacterial infection of the bile ducts, is a common complication of Caroli’s disease and Caroli’s syndrome.

Cholangitis can cause severe pain in the upper right part of the abdomen. If left untreated, cholangitis can become serious enough to be life-threatening.

Gallstones

Abnormal bile duct function can also lead to gallstones, which are painful blockages of the gallbladder.

When gallstones cause symptoms, they can cause severe pain in the upper abdominal area and back pain between the shoulder blades or below the right shoulder.

Nausea and vomiting can occur.

Renal insufficiency

Progressive cysts are closed sacs that can contain air, fluids, or semi-solid material that can resolve on their own or must be surgically removed.

These cysts progressively destroy healthy kidney tissue and can lead to decreased kidney function and kidney failure.

People who show signs of Caroli syndrome at a young age are more likely to suffer kidney damage from this condition.

Symptoms of kidney failure include an inability to regulate water and electrolyte balance, to remove waste products from the body, or to promote red blood cell production.

Symptoms also include fatigue, weakness, shortness of breath, and generalized swelling, eventually leading to multiple organ failure and death.

Liver failure

People with Caroli syndrome are prone to fibrous tissue growth in the liver, which can cause progressive damage, cirrhosis (scarring of the liver to the point where scar tissue replaces healthy tissue), and eventually total liver failure.

A damaged liver cannot remove toxins from the body, causing them to build up in the body and brain.

Also, loss of liver function can lead to liver cancer, which cannot be reversed.

Variceal bleeding

Portal hypertension (increased blood pressure in the portal vein, which carries blood from the digestive system to the liver) can cause blood vessels to spread out and be vulnerable to injury and bleeding.

Variceal bleeding is bleeding from dilated blood vessels in the esophagus or stomach that can cause profound blood loss and can cause anemia (a blood disorder that occurs when red blood cell levels become too low).

Others

There have been reports of people with Caroli’s syndrome experiencing an aneurysm, which is when a blood vessel produces a balloon-like bulge that can burst and cause death.

Treatment of Caroli’s disease

General

There is no cure for Caroli’s disease or Caroli’s syndrome. Instead, treatment aims to reduce symptoms and prevent complications.

Symptoms appear first in adults, although childhood and neonatal cases have been reported.

Mortality in Caroli’s disease is caused by complications.

After cholangitis (inflammation of the bile duct) occurs, which occurs in disease and syndrome states, large numbers of patients die within 5 to 10 years.

Antibiotics

Antibiotics such as ampicillin and sulbactam may be prescribed to treat cholangitis, a bile duct infection.

Dialysis

When the kidneys begin to fail, patients can undergo various types of dialysis to restore the filtering function of the kidneys.

In hemodialysis, a patient’s blood flows to an external filter and is cleaned.

The filtered blood is returned to the body. In peritoneal dialysis, a fluid containing dextrose is put into the abdomen through a tube.

This solution absorbs waste in the body and is then eliminated.

Kidney transplant

Some patients who experience kidney failure may undergo a kidney transplant.

Kidneys that are transplanted into patients with Caroli’s syndrome do not develop cysts, which are closed sacs that may contain air, fluid, or semi-solid material that may resolve on their own or must be surgically removed.

However, transplantation is associated with complications, including infection and the possibility of rejection of the new organ.

To reduce the chance of rejection, patients may need to take immunosuppressive medications.

Liver transplant

Some patients who experience liver failure may undergo a liver transplant.

Livers that are transplanted into patients with Caroli’s syndrome do not tend to become fibrotic or hardened.

However, transplantation is associated with complications, including infection and the possibility of rejection of the new organ.

To reduce the chance of rejection, patients may need to take immunosuppressive medications.

Surgery

Some patients with Caroli’s disease benefit from surgical drainage of the affected bile ducts, which carry bile from the liver to aid in the digestion of fats.

In more severe cases, however, this procedure may be inappropriate.

In some patients who experience severe pain, surgery may be done to shrink the cysts that grow in the kidneys.

This surgery does not provide a cure for the disease, as the cysts grow back.

Also, surgery can be used to remove portions of the liver in some people with liver fibrosis who are not candidates for transplantation.

Surgery may also be an option for treating bile duct infections that do not respond to antibiotic treatment.

People with Caroli’s syndrome, the complex form of the disorder, are about 100 times more likely than the general population to develop cholangiocarcinoma (cancer of the bile ducts), which carry bile from the liver to aid in the digestion of fats .

Cholangiocarcinoma is considered an incurable and rapidly fatal disease.

Surgery is needed to remove the tumors. However, more often than not, the disease has progressed too far for surgery to be effective by the time it is discovered.

Drugs

The ursodiol is a bile acid and can be prescribed for dissolving gallstones.

Side effects of these medications include diarrhea , severe stomach aches, nausea, and vomiting.

Ursodiol must be used for one or more years, and gallstones will return within five years in 50% of patients who have had a successful dissolution of their gallstones.

Integrative therapies

There is currently a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Caroli’s disease and Caroli’s syndrome.

Caroli’s disease prevention

Since Caroli’s disease and Caroli’s syndrome are rare inherited disorders, there are no known ways to prevent them.

Because the exact genetic mutations that cause these conditions have yet to be identified, genetic testing, including prenatal diagnostic procedures, is currently not available.

There have been reports of prenatal diagnosis using ultrasound.

Abnormalities in the bile ducts and kidneys can be examined using ultrasound technology, which allows a visualization of the fetus and its organs while in the womb.

Prognosis of Caroli disease

Management depends on the clinical presentation, location, and stage of the disease.

Quality of life can be significantly affected by recurrent cholangitis. The prognosis depends on the clinical course and the risk of cholangiocarcinoma.