Primary sclerosing cholangitis (PSC) is a disease primarily of the bile ducts, both inside and outside the liver. The ducts of the gallbladder and pancreas may also be involved. The walls of the bile ducts become inflamed and this inflammation causes scarring and hardening that narrows the bile ducts. Because bile cannot drain properly through the ducts, it accumulates in the liver causing damage to liver cells.

Eventually, so much bile is accumulated, it seeps into the bloodstream. Finally, with long term cell damage, the liver develops cirrhosis (hardening or fibrosis) and it can no longer function properly.

According to Medilexicon's medical dictionary:

Primary Sclerosing Cholangitis is an idiopathic chronic hepatobiliary disease characterized by diffuse inflammation and fibrosis of the extrahepatic biliary system resulting in patchy, irregular stricturing of the bile ducts. Progressive bile duct obliteration to cirrhosis, hepatic failure, and bile duct cancer may occur in up to 50% of patients. Frequently associated with inflammatory bowel disease.

Liver cells excrete bile into tiny tubes within the liver called bile ducts. These tubes come together like the tiny veins on a leaf. They drain the bile into the common bile duct, a larger single tube leading into the intestine. There the bile assists digestion and gives stool its brown color.

There is a strong association between primary sclerosing cholangitis and chronic ulcerative colitis. Primary sclerosing cholangitis can also occur alone or in association with Crohn's disease, a disease of the intestines that is related to ulcerative colitis. Colon cancer is also associated with PSC.

Primary sclerosing cholangitis is a rare disease with an estimated prevalence in the United States of 6 per 100,000 people. It is more common in men then in women. Approximately 70% of primary sclerosing cholangitis patients are men. The mean age at diagnosis of primary sclerosing cholangitis is around 40 years of age. What are the symptoms of Primary Sclerosing Cholangitis? A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

Most patients with early primary sclerosing cholangitis have no symptoms, and the presence of primary sclerosing cholangitis is recognized only because of abnormally elevated blood levels of liver enzymes, particularly alkaline phosphatase levels, that often are performed along with a routine physical examination.

The symptoms are caused by two things: the bile is not being drained properly through the bile ducts, and the liver is not doing its job. Bile ducts can become infected, causing chills, fever and upper abdominal tenderness. Itching may occur when bile seeps into the bloodstream. As the disease progresses, chronic fatigue, loss of appetite, weight loss and jaundice may occur. The accumulation of bilirubin turns the skin and whites of the eye yellow. These patients also are at risk of developing primary sclerosing cholangitis complications.

The reason for the pruritus is not entirely known. It may be due to accumulation of bile salts in the body, also as a result of obstruction of the bile ducts.

Finally, in the advanced stages of cirrhosis, extensive swelling can occur in the abdomen and feet. Liver failure may take many years to develop. What are the causes of Primary Sclerosing Cholangitis? The exact cause of PSC is unknown. However, the most likely cause appears to be changes in the way the immune system works. When the immune system is working properly, it protects the body from infections caused by foreign invaders like bacteria and viruses. Sometimes, however, it recognizes certain body parts or organs as foreign. The body then goes to war against itself, damaging the body part it thinks is foreign.

The disease is often seen in patients who have inflammatory bowel disease (Crohn's disease and ulcerative colitis), sarcoidosis, chronic pancreatitis and many other autoimmune disorders.

Genetic factors may also be responsible. Sclerosing cholangitis occurs more often in men than women and this disorder is rare in children. Diagnosing Primary Sclerosing Cholangitis A physician may suspect PSC from a patient's medical history, especially a history of inflammatory bowel disease, and from abnormal blood tests.

The diagnosis is usually made by cholangiography, an x-ray called ERCP that involves injecting dye into the bile ducts. These ducts are typically normal in appearance in patients with PBC, but in primary sclerosing cholangitis patients, these ducts have a beaded appearance (multiple narrowings along the ducts with areas of widening in between). The test is performed under sedation and a lighted, flexible endoscope is inserted through the mouth, stomach and then into the small intestine. A thin tube is place through the scope into the bile ducts, and the dye is injected to highlight the bile ducts on the x-ray. If there is narrowing of the bile ducts, the diagnosis of PSC is confirmed.

As the disease progresses, a liver biopsy is usually needed to determine how much damage has occurred. Under local anesthesia, a slender needle is inserted through the right lower chest to extract a small piece of liver for microscopic analysis.

Patients with primary sclerosing cholangitis have a high likelihood of also having ulcerative colitis, and patients with primary sclerosing cholangitis and ulcerative colitis have higher risks of developing colon cancer. Thus, colonoscopy is important to both diagnose ulcerative colitis and for early detection of cancer or precancerous conditions. What are the treatment options for Primary Sclerosing Cholangitis? Standard treatment includes ursodiol, a bile acid naturally produced by the liver, which has been shown to lower elevated liver enzyme numbers in people with PSC, but has not improved liver or overall survival.

Treatment also includes medication to relieve itching (antipruritics), bile acid sequestrants (cholestyramine), antibiotics to treat infections, and vitamin supplements, as people with PSC are often deficient in vitamin A, vitamin D, vitamin E and vitamin K.

Actigall is a drug that favorably changes the make-up of bile in the liver. This, in turn, seems to reduce the amount of liver damage that occurs. If ulcerative colitis is also present, it is treated with the appropriate medicines.

Swelling of the abdomen and feet, due to fluid retention from cirrhosis, can be treated with a salt-restricted diet and diuretics. Presently, there are exciting studies being done to test the effectiveness of other drugs on the body's immune system, since this seems to be the underlying problem.

In some cases, endoscopic or surgical procedures may be used to open major blockages in bile ducts. Through an endoscope, the physician places a tiny tube with a balloon on the end into the narrowed bile duct. The balloon is inflated to expand the duct so bile can flow through it once again. Sometimes stents (plastic tubing) can be placed in the narrowed ducts to keep them open.

Often PSC progresses to a point where liver transplantation must be considered. Liver transplantation is now an accepted form of treatment for chronic, severe liver disease. Advances in surgical techniques and the use of new drugs to suppress rejection have improved the success rate of transplantation. The outcome for PSC patients is excellent. Survival rates at transplant centers are well over 90 percent, with a good quality of life after recovery. Preventing Primary Sclerosing Cholangitis As with most liver diseases, prevention of PSC consists of avoiding alcohol and maintaining a healthy diet.

Sy Kraft (B.A.)