Primary Sclerosing Cholangitis

What is primary sclerosing cholangitis?

Primary sclerosing cholangitis (PSC) is a disease of the bile ducts. It causes chronic inflammation in your bile ducts (cholangitis), which eventually causes scarring (sclerosis). Scar tissue in your bile ducts causes them to narrow, which restricts the flow of bile through the ducts (biliary stricture). When bile can’t flow, it backs up into your liver, where it came from. This does progressive damage to your liver.

Is primary sclerosing cholangitis serious?

Yes. While you might not have symptoms at first, PSC is a progressive disease that gets worse over time. When bile stalls in your bile ducts (cholestasis), it can begin to leak bile toxins into your bloodstream, which makes you sick. It also does progressive damage to your liver. Within 10 to 15 years, this can lead to liver failure. You can’t live without a liver. While there are temporizing treatments, there is currently no cure for PSC, except a liver transplant.

What is the difference between primary sclerosing cholangitis and secondary sclerosing cholangitis?

“Primary” means that this disease is the original cause of inflammation and scarring of your bile ducts. There’s no other cause but the disease. In secondary sclerosing cholangitis, inflammation (cholangitis) and scarring (sclerosis) of your bile ducts are secondary effects caused by something else. Some causes of secondary sclerosing cholangitis include:

• Bile duct injury (for example, during surgery).
• Infections of the bile ducts.
• Chemotherapy.
• Gallstones in your bile ducts.
• Recurring pancreatitis.

What is the difference between primary biliary cirrhosis and primary sclerosing cholangitis?

Primary biliary cholangitis (PBC) is the current name for what was previously called primary biliary cirrhosis.

PBC and PSC are both progressive bile duct-related liver diseases, with similar symptoms and effects. Both diseases cause the gradual deterioration of your bile ducts. Destruction and scarring in your bile ducts cause them to narrow and the flow of bile to stall. The bile begins to back up into your liver, where it causes further damage. This leads to scarring and eventually, cirrhosis of the liver.

Here are the primary differences:

• PBC only affects the bile ducts within your liver (intrahepatic), while PSC can affect the bile ducts inside or outside of your liver (extrahepatic).
• PBC is more predominant in people assigned female at birth, by a ratio of 10:1. PSC is more predominant in people assigned male at birth, by a ratio of 2:1.
• PSC is highly associated with preexisting IBD (80%), while PBC is not.
• PSC is associated with an increased risk of developing bile duct cancer, while PBC is not.
• PBC treatment involves using ursodeoxycholic acid (UDCA) to slow its progression. PSC currently has no medical treatment.

How common is this condition?

PSC is rare. It’s estimated to occur in about 1 in 10,000 people worldwide.

Who does it affect?

PSC occurs in people assigned male at birth twice as often as in people assigned female at birth. It’s most often diagnosed around the age of 40. About 80% of people with PSC also have inflammatory bowel disease, most often ulcerative colitis. It’s more likely to occur in people with a family history of the disease.

What causes primary sclerosing cholangitis?

It’s not entirely clear, but it appears to involve a combination of factors, including:

• Genetics.
• Environment.
• Immune cells.

Doctors believe that PSC may be a type of autoimmune disease. That means it causes your body’s immune system to attack healthy cells as invaders. Inflammation is one of the tools of your immune system. It’s supposed to be an acute response to an attack, but when inflammation becomes chronic, it tends to be a sign of disease.

Doctors have also noticed that people who have PSC are prone to other autoimmune diseases, including:

• Inflammatory bowel diseases.
• Celiac disease.
• Thyroid disease.
• Type 1 diabetes.
• Autoimmune hepatitis.
• Autoimmune pancreatitis.

It appears that certain environmental factors (such as toxic exposure) may trigger an autoimmune response in people with certain genetic profiles.

What are the signs and symptoms of primary sclerosing cholangitis?

The signs and symptoms of PSC change as the disease becomes more advanced. Up to 50% of people may have no symptoms at all at the time of diagnosis. PSC is often found by accident when testing for other conditions. The first symptoms to develop tend to be vague. They may include:

• Fatigue.
• Upper right quadrant abdominal pain.
• Itchy skin (pruritus).

Later-stage symptoms may include:

• Swollen abdomen.
• Enlarged liver.
• Enlarged spleen.
• Jaundice.
• Fever.
• Unintended weight loss.

What are the complications of advanced PSC?

Primary sclerosing cholangitis is a slow progressing disease. But as your bile ducts and liver become increasingly scarred, their functions will increasingly fail. This can lead to:

Metabolic diseases

When your bile ducts become significantly blocked, they won’t be able to deliver bile to your small intestine to help with digestion as they normally would. Bile is necessary to help break down fats in your intestines and to absorb fat-soluble vitamins (A, D, E and K). Without it, your digestive system may have trouble processing fats, and you may not be able to absorb these essential vitamins from your food. This can lead to a variety of additional complications, including:

• Fatty stools and diarrhea.
• Malabsorption and malnutrition.
• Easy bruising and bleeding (vitamin K deficiency).
• Osteomalacia and osteoporosis (vitamin D deficiency).
• Poor night vision.

Portal hypertension

Progressive cirrhosis of the liver reduces blood flow through your liver, which increases pressure in the portal vein that runs through your digestive system. This pressure causes other veins in your esophagus and abdomen to enlarge and makes them vulnerable to bursting, which can cause internal bleeding.

Infections

Blocked bile ducts are prone to frequent infections, which may cause fever, abdominal pain, blood infection or sepsis.

Cancer

Advanced PSC leads to an increased risk of developing several cancers, including:

• Bile duct cancer (cholangiocarcinoma between 5% and 20%).
• Gallbladder cancer.
• Liver cancer (hepatoma).
• Colorectal cancer (if you also have IBD).

How is primary sclerosing cholangitis diagnosed?

It’s often found by accident while testing for something else. Up to 50% of people may not have any symptoms at the time of diagnosis. Early signs of the disease may show up on a blood test or imaging test. Images of bile ducts with PSC show certain distinctive features. A blood test may show high levels of alkaline phosphatase or certain antibodies that indicate an immune response in your bile ducts. White blood cell elevation is usually a sign of infection in the liver.

To confirm the disease, your healthcare provider may suggest a more specific test, such as a:

• Liver function test. These blood tests look for high levels of particular liver enzymes. High levels of alkaline phosphatase may indicate PSC.
• Magnetic resonance cholangiopancreatography (MRCP). This test uses magnetic resonance imaging (MRI) to produce detailed pictures of the biliary tree (your liver, gallbladder and bile ducts). This is the first-line imaging test for PSC because it’s non-invasive and avoids radiation exposure. Occasionally, it might not reveal an early or mild case of the disease, and you might need another kind of imaging test.

How is primary sclerosing cholangitis treated?

Currently, there is no treatment that can slow or stop primary sclerosing cholangitis from progressing. You can treat some of the symptoms and complications directly. For example, your healthcare provider may prescribe:

• Medications to treat itchy skin (pruritus).
• Supplements to treat vitamin deficiencies.
• Antibiotics to treat infections.

Your healthcare provider will also keep your liver and bile ducts under surveillance. As the disease progresses, they may be able to periodically intervene by opening up a blocked bile duct. They can do this through an ERCP (endoscopic retrograde cholangiopancreatography), a type of exam that allows access to your bile ducts without surgery.

An ERCP is a type of endoscopy, which means it examines your organs using an endoscope, a tiny lighted camera attached to a long, flexible tube. Under anesthesia, your healthcare provider advances a tube down your throat into your abdominal cavity. They can pass tiny instruments through the tube to treat your bile ducts. Your technician can dilate your bile duct with a balloon, or prop it open with a stent. If the blockage is not accessible by ERCP then they obtain access directly through the skin, a procedure called percutaneous trans-hepatic cholangiography (PTHC).

This is a temporary solution, however. Over the course of 10 to 20 years, primary sclerosing cholangitis eventually progresses from early to late-stage liver disease, and finally, liver failure. Your healthcare provider will monitor your liver damage to determine when you should begin to consider liver transplantation. You’ll need to pass certain qualifications to get on a liver transplantation waiting list.

What is the life expectancy with primary sclerosing cholangitis?

After diagnosis, the average life expectancy ranges between 10 and 20 years. A liver transplant can give you a new lease on life. However, in 15% to 20% of cases, PSC may return after a liver transplant. When this happens, the new liver may fail. The average life expectancy in this case is about nine months.

Another factor that can affect life expectancy is cancer. If cancer develops as a complication of PSC, you may not be a good candidate for a liver transplant. In carefully selected cases, healthcare providers may attempt to treat cancer first with radiation or chemotherapy and then attempt a liver transplant.

How should I take care of myself if I have this disease?

Lifestyle choices can help to manage the fatigue that’s common with PSC and prevent additional damage to your liver. For example:

• Avoid alcohol.
• Eat more whole foods and less processed foods.
• Manage stress.
• Get plenty of sleep.
• Exercise a little each day.

A note from Cleveland Clinic

Primary sclerosing cholangitis is rare, unpredictable and unpreventable. It progresses slowly and often without early symptoms. But if you visit your healthcare provider periodically for routine screenings, you may discover it well before it begins to affect your life. This is your chance to implement lifestyle choices that may help to preserve the health of your liver longer. You’ll also begin the process of long-term medical maintenance, including regular testing and interventions when necessary.