The Intractable Hepato-Biliary Diseases Study Group in Japan, Health Labor Science Research Grants from Research on Measures for Intractable Diseases


Primary Sclerosing Cholangitis

Last Update: February 22, 2022

1. What kind of disease is it?

Bile, which is involved in the digestion and absorption of foods, is produced by the liver in approximately one liter per day and secreted via ducts known as bile ducts. Bile travels through small bile ducts within the liver, and when the stomach is empty, it becomes concentrated in the gall bladder. Then, when the gall bladder is stimulated to contract by the act of eating (food intake), bile is secreted through a thick bile duct into the duodenum. If the bile ducts are not functioning properly, the bile flow is disrupted, and jaundice can occur.
Primary sclerosing cholangitis (PSC) is a disease that causes narrowing of the bile ducts, which has a negative effect on their ability to function properly. As a result, the flow of bile is disrupted, and liver functions are negatively affected. One characteristic of PSC is damage to the relatively thick bile ducts within and external to the liver. As is the case with another disease that damages the bile ducts, PBC, blood tests show elevated levels of ALP and γGTP. However, as there are no characteristic auto-antibodies, it is impossible to diagnose this disease based on a blood test alone. Usually, it is diagnosed using cholangiography modalities such as ERCP and MRCP.
PSC is often complicated with ulcerative colitis, Crohn's disease, and other inflammatory bowel diseases. There is a particularly high number of young patients. It has been reported that approximately 40% of all PSC patients in Japan and 60% of the young patients in Japan suffer from inflammatory bowel disease as a complication. Ulcerative colitis is a common inflammatory bowel disease that appears as a complication of PSC, but there are also cases of atypical colitis that are not diagnosed as either ulcerative colitis or Crohn's disease.

2. How many people are affected by this disease?

An epidemiological study conducted in 2007 estimated that the total number of patients with PSC in Japan was approximately 1,200. However, a 2018 survey estimated the number to be 2,300 patients, indicating that the number almost doubled over ten years. The number of patients with PSC is also increasing around the world.

3. What sort of people are susceptible to this disease?

Males are slightly more likely to develop the disease, and in terms of age at onset, there are two peaks: one in the twenties and the other in the sixties. It is not unusual for disease onset to occur in teenagers, and the abovementioned national study found that 55 patients under the age of 18 were registered as having the disease.

4. Are the causes of this disease known?

The causes are not yet known. Hypotheses regarding the cause of the disease that are based on the fact that inflammatory bowel disease is a complication have been proposed. These include the possibility that enteric bacteria enter the liver through inflamed large intestine mucosa and the possibility that lymphocytes in the large intestine are abnormally activated, flow into the liver, and cause damage to the bile ducts. However, a clear cause has yet to be identified. In addition, antinuclear antibodies are detected in approximately 30% of patients, suggesting that autoimmunity may be involved.

5. Is this disease hereditary?

It is not hereditary. However, as is the case with other autoimmune diseases, it is known that there is a genetic influence on the onset of PSC, as several genes that are involved in PSC onset have been identified outside of Japan.

6. What are the symptoms of this disease?

In many cases, PSC is associated with jaundice and itchiness. However, there are also asymptomatic cases discovered and diagnosed only when abnormalities in liver function test results or abdominal ultrasound examinations are identified as part of a regular medical checkup or detailed medical examination. In some cases, the disease progresses after diagnosis without the appearance of any symptoms, but it is common for patients to experience symptoms such as jaundice and skin itchiness because of narrowing of the bile ducts, which disrupts the flow of bile, or cholangitis as a result of microbial infection. If PSC remains undiagnosed and no treatment is provided, or treatment has little effect, then the abovementioned symptoms will occur repeatedly, liver functions will gradually decrease, and the disease progresses to cirrhosis of the liver. As a result, as is the case with cirrhosis due to other causes, the patient will develop esophageal or gastric varices, ascites, jaundice, and hepatic encephalopathy, the disease will progress to liver failure, and if liver transplantation is not performed, it may be impossible to save the patient. Besides, it is known that cholangiocarcinoma is a complication of PSC.

7. How is this disease treated?

In Japan, in many cases, ursodeoxycholic acid is utilized, as this drug reduces ALP and γGTP levels. However, when this drug fails to reduce levels sufficiently, it has been established that the additional administration of bezafibrate will further lower ALP and γGTP levels. Further study is required to determine whether the use of these drugs will suppress PSC progression itself and improve long-term prognosis as insufficient data is currently available. In addition, in cases in which cholangiography indicates a marked narrowing of the bile ducts, endoscopic cholangiectasis (dilation of the bile ducts) is performed. In cases where the disease has progressed to liver failure, liver transplantation is the only treatment option. In Japan, the number of brain-dead donor liver transplantations is low, as in most cases, live donor segmental liver transplantation is performed.

8. What is the course of this disease?

In cases in which the disease progresses without symptoms, ursodeoxycholic acid administration can lead to a satisfactory disease course. If PSC is not diagnosed and no treatment is provided or in cases in which treatment has little effect, the disease will progress to cholangitis, which produces symptoms such as fever and abdominal pain, and jaundice will appear. Eventually, the disease will progress to cirrhosis of the liver. Intra-liver cholangiocarcinoma is a known complication. Liver transplantation is effective in cases that progress to this point. The postoperative five-year survival rate is good at 75%. However, postoperative recurrence is not uncommon.
According to a 2015 national survey of all PSC patients in Japan, the five-year and ten-year survival rates after PSC diagnoses were 81.3% and 69.9%, respectively, and the five-year and ten-year survival rate in cases in which liver transplantation was not performed were 77.4% and 54.9%, respectively. However, when limited to patients who had no symptoms at the time of diagnosis, the five-year and ten-year survival rates were 87.3% and 66.5%, respectively, and when limited to young patients who had no symptoms at the time of diagnosis were 91.3% and 73.5%, respectively.

9. What precautions in daily life are required?

Patients must have blood tests and imaging studies done during regular visits to their doctors and take their prescribed medication. Since this is a rare disease, patients should be examined by a specialist who is knowledgeable in PSC and undergo regular examinations. Even in cases where regular visits are difficult, patients should be examined once by a specialist and discuss the current disease status, future prospects, and treatment strategy.
If there are no symptoms, then no particular precautions are required in daily life, and rest is not required. The patient can work, do housework, exercise, and eat normally. In cases in which the disease progresses to cirrhosis of the liver, careful precautions in daily life, including diet and exercise, are required. Such patients should consult with their attending physician.

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