Caroli disease is the name given to a rare disease of the bile ducts. In it, affected individuals often suffer from inflammation and gallstones in the bile ducts.
What is Caroli disease?
Caroli disease is a very rare bile duct disease that is already congenital. It involves a marked dilatation of the large bile ducts within the liver. A typical feature of the disease is frequent inflammation and the formation of stones within the bile ducts. Caroli’s disease was named after the French gastroenterologist Jacques Caroli (1902-1979), who first described it in 1958. Physicians differentiate the disease between Caroli disease and Caroli syndrome, which is based on the bile ducts involved. Caroli syndrome is more common and is associated with congenital liver fibrosis. In contrast, Caroli disease presents more often and occurs in the intrahepatic ducts without an increase in connective tissue. In principle, Caroli disease can break out at any age. The female sex is particularly affected by the disease. Caroli disease is one of the rare diseases. Thus, only about 250 cases have been registered in the world so far.
Causes
What causes Caroli disease has not yet been determined. As a rule, it manifests itself sporadically. Numerous medical experts suspect genetic triggers. Thus, autosomal recessive inheritance takes place in Caroli syndrome. Normally, there is a balance in the expression of vascular endothelial growth factor receptors type 1 and 2 (VEGFR 1 and 2) and vascular growth factor (VEGF). However, if Caroli disease occurs, this leads to mutation of the PKHD-1 gene, which in turn results in disruption of molecular signaling pathways. Thus, endothelial growth factor as well as its growth factor receptors are overexpressed by cholangiocytes, which produce about one-third of bile. In this process, VEGF causes proliferative effects on cholangiocytes. This creates an obstruction to the outflow of bile. Furthermore, vascular endothelial growth factor causes dilation of bile ducts due to cholangiocyte proliferation by autocrine effects. Cholangiocyte activation occurs by an independent mechanism. The intrahepatic bile ducts are normally supported by type 4 collagen and laminin. However, in the case of Caroli disease, degradation of these components occurs. A loss of the supporting effect is then the result.
Symptoms, complaints, and signs
It is not uncommon for Caroli disease to progress with only sporadic symptoms or even no symptoms at all during the first 5 to 20 years of life. These can vary widely and depend on the triggering genetic mutation as well as the age of onset of the disease. Autosomal recessive polycystic kidney disease]] is present in about 60 percent of all patients. Thus, the same genetic mutation exists in both diseases. The most common symptoms of Caroli disease include chills and fever due to cholangitis (inflammation of the bile ducts). In addition, affected individuals often suffer from pain in the right upper abdomen. The pain and swelling of the gallbladder are caused by a backlog of bile. As the disease progresses, there is a risk of gallstones forming. Dilatation of the intrahepatic bile ducts can also lead to hepatomegaly, in which the liver becomes abnormally enlarged. If the bile drainage is blocked, patients often suffer from itching. The insufficient outflow causes chenodeoxycholic acid to accumulate, which in turn triggers severe itching. In the worst case, there is a risk of liver fibrosis and, in the further course, life-threatening liver cirrhosis. In addition, the risk of developing bile duct carcinoma increases.
Diagnosis and course
If Caroli disease is suspected, the physician uses imaging techniques to make a diagnosis. Crucial to determining the disease in both Caroli disease and Caroli syndrome is a connection between the bile ducts and cysts in the liver.These compounds can be detected by ultrasonography (sonography), hepatobiliary function scintigraphy, computed tomography (CT), or magnetic resonance cholangiopancreatography (MRCP). The course of Caroli’s disease depends on how often bile duct infections occur. If they occur more frequently, this has a negative effect on the prognosis. This means that the quality of life is already impaired at an early age. Furthermore, there is a risk of complications such as liver abscesses and liver cancer.
When should you go to the doctor?
If chills, cholangitis, and other signs of Caroli disease occur, a doctor should be consulted in any case. If symptoms of cirrhosis of the liver are added, this requires immediate evaluation by a medical professional. In the event of further complications such as liver abscesses and signs of liver cancer, this is a medical emergency – the nearest clinic must be visited immediately. The same applies if severe pain, gastrointestinal complaints or infections occur, which massively reduce the quality of life. In addition, since Caroli disease has genetic factors, a doctor should be consulted if there are already cases of the disease in the family, if there are other genetic diseases, or if the family history shows several cases of liver and organ diseases. In addition to the family doctor, a specialist in genetic disease or – if there are sudden severe symptoms or serious complications – the emergency medical service can be consulted. Accompanying therapeutic counseling is sometimes useful, especially if Caroli disease is associated with psychological complaints such as depression.
Complications
As a rule, complications of Caroli disease occur mainly in the bile ducts. Gallstones may deposit there or inflammation may develop. In most cases, Caroli disease results in relatively severe pain that interferes with the patient’s daily life. The kidneys are also negatively affected by Caroli disease. Most patients complain of symptoms of flu, such as fever or chills. The quality of life decreases due to Caroli’s disease. Pain occurs mainly in the upper abdomen and the gallbladder swells. If the bile is unable to drain, there is usually severe itching, which is further exacerbated by the patient scratching. In most cases, treatment regulates the outflow of bile and is carried out with the help of antibiotics. There are no further complications in this process. If the pain in the abdomen does not disappear, surgery must be performed. This is associated with complications that depend on the age of the patient. If Caroli’s disease is not treated, the risk of cancer increases. However, with early detection and treatment, there are no further complications or symptoms.
Treatment and therapy
Therapy for Caroli disease or Caroli syndrome depends on the age of the person with the disease. In addition, it is important at which sites and to what extent bile outflow obstructions occur. If the patient suffers from bacterial infections of the bile ducts, he is given broad-spectrum antibiotics. Cholestyramine is usually administered to treat itching. To treat gallstones, ursodeoxycholic acid or drugs with similar effects can be used. Pain in the upper abdomen caused by cholecystitis can be subjected to both conservative and surgical therapy. In the context of surgical intervention, doctors usually prefer minimally invasive surgery. If only a single lobe of the liver has been affected by the disease, it can be partially removed by hepatectomy. This also reduces the risk of developing cancer. If Caroli’s disease has already progressed, a liver transplant can be performed. This extensive procedure can also reduce the risk of bile duct cancer in the long term. The
Survival rate with this procedure is considered high.
Outlook and prognosis
The prognosis of Caroli disease depends on several factors and is individualized for each patient. The hereditary disease is inherited in a recessive manner and may also have a fatal course, depending on the sequelae.The patient is at very high risk of developing bile duct carcinoma. The cancer may result in the patient’s demise or be associated with lifelong impairments. Approximately 90% of those with cholangiocarcinoma die within a few years of diagnosis. The prognosis of Caroli’s disease worsens the more frequently the patient experiences inflammation of the bile duct. The intensity of the inflammation also affects the healing process. Women who rarely experience cholangitis to a low degree have the best chance of relief. A stable immune system is also particularly supportive, so that the inflammation can be fought quickly and without complications. In these patients, a cure for Caroli disease is possible. In 60% of patients, kidney disease is diagnosed as the disease progresses. This leads in the long term to renal insufficiency and later to renal failure. Caroli disease resolves episodes of symptoms over several years. This places a high emotional and psychological burden on the patient.
Prevention
Preventive measures against Caroli disease are not known. Thus, the condition is already congenital.
Aftercare
In most cases, patients with Caroli disease have no options for follow-up care. The disease must be treated symptomatically to prevent further complications and worsening of the overall condition. It is also possible that the life expectancy of the affected person is reduced by Caroli disease. In this case, early treatment and diagnosis of the disease have a very positive effect on the further course of the disease. In most cases, Caroli disease is treated by taking antibiotics. The patient must ensure that the medication is taken regularly. Alcohol must be avoided, although interactions with other medications should also be taken into account. In this case, however, consultation with a physician is necessary. Since Caroli disease also increases the risk of cancer, regular examinations are advisable in order to detect and treat tumors at an early stage. Since the disease can also be treated by surgery, the affected person should rest and take care of the body afterwards. Athletic activities and other strenuous activities should be avoided. Since the disease can often lead to psychological complaints or depression, it is also useful to talk to friends and acquaintances. Contact with other people affected by Caroli’s disease can also be useful.
What you can do yourself
Because Caroli disease is a congenital condition, there is no causative treatment available. People who are diagnosed with the condition do not experience any symptoms or discomfort at first and should simply focus on paying attention to their body’s signals in the beginning. If unusual symptoms occur, a doctor must be informed who can clarify the complaints. The hereditary disease is associated with a greatly increased risk of developing bile duct carcinoma. Patients should therefore watch carefully for unusual symptoms and a potentially severe course. Since the prognosis worsens with each inflammation of the bile duct, appropriate preventive measures are indicated. Affected individuals should strive for a healthy lifestyle with adequate exercise and a balanced diet. Risk factors such as colds or stress should be reduced. Should inflammation nevertheless occur, it must be treated quickly. In the best case, this can prevent the development of a carcinoma. In the case of renal insufficiency, the patient must take it easy and change his diet in cooperation with the doctor. Since Caroli disease is also mentally grueling, therapeutic advice should be sought. The physician in charge can also establish contact with other sufferers.
