Primary Sclerosing Cholangitis (PSC)

Primary sclerosing cholangitis describes a disease process in which the bile ducts in the liver become inflamed, narrow and prevent bile from flowing properly.

The liver produces bile to help digest food in the intestine. Bile from liver cells is transported through the bile ducts in the biliary tree, where it then enters the gallbladder. When food enters the small intestine, bile helps break down fat into fatty acids so that they can be absorbed and used by the body. This also helps in the absorption of fat-soluble vitamins (A, D, E & K).

As the bile ducts become inflamed and narrow, bile cannot easily flow and begins to back up. This increases the pressure within the liver causing liver cells to become inflamed. Over time, this inflammation decreases blood flow within the liver, increasing the pressure in the portal vein. This eventually causes portal hypertension, a backup in the portal system causing veins that line the esophagus, stomach, and intestine to swell (varices) and the spleen to swell (splenomegaly).

As the disease progress, liver cells die and are replaced by scar tissue. This is called cirrhosis and is associated with liver failure.

The cause of PSC is unknown but it has an association with inflammatory bowel disease, especially ulcerative colitis. It is thought that there may be an autoimmune component to the disease, where the body's immune system attacks the bile ducts in the liver and causes them to become, inflamed and narrowed.

The cause of PSC is unknown but it may be an autoimmune disease.

PSC is more often seen in men in the 20-30 age range. There is an association with inflammatory bowel, disease, most often with ulcerative colitis and less commonly with Crohn's Disease.

People with PSC who do not have inflammatory bowel disease, are more likely to be female and older.

In its early stages, PSC is asymptomatic (there are no symptoms). It is only when the person develops cholestasis because of the inability of bile to drain from the liver, do symptoms occur. These early symptoms include itching and fatigue. As the bilirubin levels in the blood become elevated, jaundice or a yellowish tinge to the skin may occur. Since there may be liver inflammation, the person may complain of pain beneath the ribs in the right upper quadrant of the abdomen.

The inability of the bile ducts to adequately drain reduces the flow of bile and there can be sludge formation in the bile ducts leading to the risk of infection. This may cause fever and increased pain.

Because PSC is a progressive disease, symptoms may come and go over several months and years after the diagnosis is made.

As the disease progresses, cirrhosis may occur leading to decreased liver function and its associated signs and symptoms. These include bleeding from the esophagus and stomach due to varices, ascites (fluid collection in the abdomen) because of poor protein production by the liver, easy bruising because of decreased platelets in the blood because they are trapped in the enlarged spleen, and confusion due to hepatic encephalopathy because the liver cannot clear waste products of metabolism.

PSC may remain silent for several years before symptoms arise. In patients with inflammatory bowel disease, the healthcare professional should have a high suspicion of the diagnosis because of the relationship between PSC and ulcerative colitis.

Depending upon how far the disease has progressed and the effect on liver function, a physical examination may reveal an enlarged liver, tenderness in the right upper quadrant beneath the ribs, and an enlarged spleen. The skin may be jaundiced or yellow and there can be evidence of scratching due to intense skin itching. In cirrhosis with end-stage liver disease, there may be bruising of the skin, a swollen abdomen due to ascites or fluid caused by decreased protein production and decreased blood flow through the scarred liver, gastrointestinal bleeding, and mental confusion because of elevated ammonia levels in the bloodstream.

Blood tests help assess the liver and potential blockages within the bile ducts. These may include a complete blood count, INR/PTT (that measures blood clotting and the ability of the liver to produce clotting factors), liver function studies including AST, and ALT to assess liver inflammation, alkaline phosphatase, and bilirubin which measure the degree of bile blockage.

Imaging tests may include ultrasound to look at the liver structure and magnetic resonance cholangiogram, an MRI of the abdomen that can assess the bile duct structure of the liver.

If the diagnosis based on laboratory tests and imaging is still in doubt, a biopsy may be performed. A gastroenterologist or interventional radiologist will place a long, fine needle through the skin into the liver to obtain a piece of tissue. This is analyzed under a microscope by a pathologist to make the diagnosis.

The treatment of PSC is supportive, monitoring the progression of the disease and treating symptoms and complications as they arise. The only "cure" is liver transplantation, which may be an option when the disease progresses to cirrhosis and the liver function is affected.

When some of the larger bile ducts become blocked, there is potential to open them with ERCP (endoscopic retrograde cholangiopancreatography) and balloon dilatation and/or stent placement. A gastroenterologist passes a thin video endoscope into the mouth and threads it through the stomach into the duodenum and using a catheter, enters the bile ducts. Should a narrow duct or stricture be found, a balloon can be used to dilate the narrowing and a stent can be placed to keep the duct open. This is similar to how a cardiologist opens a blocked blood vessel in the heart

In some cases, surgery may be an option to remove some scarred and blocked bile ducts and have more normal bile ducts reconnected bypassing scarred areas of the bile ducts.

No medication is approved to treat primary sclerosing cholangitis, but medications may be used to control symptoms. Ursodiol (Actigal), also known as ursodeoxycholic acid (UDCA), may improve liver function tests but has not been shown to increase survival and may be associated with complications like bleeding. While it is thought that PSC may be an autoimmune disease, immunosuppressive medications have not been shown to work.

Itching is often treated with antihistamines including diphenhydramine (Benadryl), hydroxyzine (Atarax), and cyproheptadine (Periactin). Cholestyramine (Questran, Questran Light), a medication that helps bind bile salts may also be helpful.

Should an infection occur, treatment may require antibiotics.

As the disease progresses, the damaged liver may not be able to help with the absorption of vitamins and nutrients from the intestine. Vitamins and other dietary and calorie supplements may be required to treat malnutrition.

A liver transplant is the only "cure" for primary sclerosing cholangitis, but it is only recommended for patients whose disease has progressed to liver failure. The three-year U.S. survival rate for all transplants is 81%. The five-year survival rate is about 75%, according to the data from the Scientific Registry of Transplant Recipients.

The goal of liver transplantation is to restore liver function. Though unlikely, PSC can recur in the new liver.

Aside from liver transplantation, there are no effective treatments for PSC. In the US, studies suggest that life expectancy ranges from 9 to 18 years if the patient does not undergo liver transplantation. Using different population study models, researchers in the Netherlands concluded that life expectancy may be longer than 21 years from the time when the diagnosis is made.

The prognosis and life expectance is poorer in older patients, those who have an enlarged liver and spleen, and in patients who are persistently jaundiced with elevated bilirubin levels in their bloodstream.

PSC is a progressive disease that damages the bile ducts and reduces the bile flow, ultimately leading to portal hypertension, cirrhosis, and liver failure.

Some cancers are associated with primary sclerosing cholangitis including gallbladder cancer, hepatocellular cancer (cancer of the liver cells), and cholangiocarcinoma (cancer of the bile ducts). The combination of inflammatory bowel disease and PSC increases the risk of developing cancers of the colon and rectum

The specific cause of PSC is still unknown and therefore it seems not to be preventable. It is appropriate for patients with inflammatory bowel disease (especially ulcerative colitis) and their health care professional to be aware of the relationship with primary sclerosing cholangitis, in case symptoms suggestive of the disease arise. However, PSC is seen in only 3% of patients with inflammatory bowel disease.