Primary Sclerosing Cholangitis (PSC)

What happens in PSC

Bile is made in the liver and flows through a branching network of bile ducts to the small intestine, where it helps digest fats. In PSC, inflammation causes scarring (fibrosis) around the ducts. Over years, the ducts develop strictures (narrowings) and areas of widening, giving a "beaded" appearance on imaging. Bile flow slows (cholestasis), damaging liver cells and eventually causing cirrhosis.

The cause is unknown. It is thought to involve immune system dysfunction, genetic predisposition and signals from the gut, which may explain the strong link with inflammatory bowel disease.

PSC and inflammatory bowel disease

About 70 percent of people with PSC have inflammatory bowel disease, most often ulcerative colitis, and less often Crohn's disease. The IBD may be mild and is sometimes diagnosed only after PSC is found. Conversely, a small percentage of people with ulcerative colitis develop PSC. Anyone with IBD and abnormal liver tests should be checked for PSC.

Symptoms

Many people are diagnosed through abnormal liver blood tests before they have symptoms. When symptoms develop, they include:

• fatigue
• itching (pruritus), often intense
• yellow skin and eyes (jaundice)
• discomfort in the upper right belly
• episodes of fever, chills and pain (bacterial cholangitis)
• weight loss

With advanced cirrhosis:

• swelling of the belly and legs
• easy bruising and bleeding
• confusion
• vomiting blood from swollen veins in the esophagus

Diagnosis

• liver blood tests: raised alkaline phosphatase and GGT, a pattern typical of bile duct disease
• MRCP (magnetic resonance cholangiopancreatography): a special MRI showing the bile ducts. This is the main diagnostic test
• ERCP: a camera procedure through the mouth to the bile ducts, used mainly for treatment or to sample strictures
• liver biopsy: occasionally, particularly for small-duct PSC, which affects only the tiny ducts
• colonoscopy to look for IBD
• elastography (FibroScan) to measure liver stiffness

Conditions that look similar

Secondary sclerosing cholangitis from bile duct stones, surgery, infections or IgG4-related disease, primary biliary cholangitis (which mainly affects women and small ducts, with positive AMA antibodies), and autoimmune hepatitis. Blood IgG4 is checked to rule out IgG4-related disease, which responds to steroids.

Treatment

No medicine has been proven to slow PSC or improve survival. Care focuses on:

Symptom relief

• itching: cholestyramine, rifampicin, naltrexone or sertraline
• fatigue: addressing sleep, mood and other causes
• vitamin supplements (A, D, E, K) if absorption is poor
• bone health: calcium, vitamin D and bone density checks

Treating complications

• ERCP with balloon dilation or stents for dominant strictures causing jaundice or infections
• antibiotics for bacterial cholangitis
• management of cirrhosis complications

Ursodeoxycholic acid

Ursodiol improves liver blood tests in some people but has not been shown to improve survival. High doses can be harmful. Some specialists use moderate doses case by case.

Cancer surveillance

PSC increases the risk of several cancers:

• cholangiocarcinoma (bile duct cancer): imaging (MRI or ultrasound) and tumor marker CA 19-9 are often done every 6 to 12 months
• gallbladder cancer: gallbladder polyps are monitored or removed
• colorectal cancer: yearly colonoscopy for people with PSC and IBD
• liver cancer in cirrhosis

Liver transplant

The only treatment that can cure advanced liver disease. It is considered for cirrhosis, repeated cholangitis, severe itching or early bile duct cancer in select centers. Results are good, though PSC can recur in the new liver in some people.

Clinical trials

Several new medicines are being studied, and joining a trial may be an option.

Outlook

PSC varies widely. Some people have slowly progressive disease for decades, while others progress faster. Average time to needing a transplant or serious complication has been estimated in the range of 10 to 20 years from diagnosis, and outcomes with transplant are good. Regular monitoring catches complications early.

Frequently asked questions

What are the first symptoms of PSC?

Many people have no symptoms at diagnosis and are found through abnormal liver blood tests. Early symptoms, when present, include fatigue, itching and discomfort in the upper right belly. Jaundice and fevers come later.

Is PSC related to ulcerative colitis?

Yes. About 70 percent of people with PSC have inflammatory bowel disease, most often ulcerative colitis. People with ulcerative colitis and abnormal liver tests should be checked for PSC.

What is the life expectancy with PSC?

It varies greatly. Many people live for decades after diagnosis. On average, a transplant or major complication may be needed 10 to 20 years after diagnosis. Liver transplant offers good long-term survival.

Can PSC be cured?

There is currently no medicine that cures PSC or stops it progressing. Liver transplant can treat advanced disease, though PSC can recur. Research into new treatments is active.