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Primary Sclerosing Cholangitis (PSC)

Primary sclerosing cholangitis (PSC) is a rare, long-term liver disease in which inflammation damages the bile ducts inside and outside the liver. Over time, this inflammation leads to scarring and narrowing of the bile ducts, which restricts the flow of bile. As the condition progresses, liver function gradually declines, affecting the body’s ability to process nutrients and remove toxins from the blood.

PSC is uncommon, affecting approximately 1 in 10,000 people. It is frequently associated with inflammatory bowel disease (IBD), particularly ulcerative colitis. Individuals with PSC face an increased risk of serious complications, including liver failure as well as cancers of the bile ducts, gallbladder, and colon. Management typically involves regular monitoring of liver function and treatment of symptoms. In some cases, procedures can help temporarily relieve bile duct blockages, but liver transplantation remains the only definitive treatment for advanced disease.

Several other conditions affecting the bile ducts can resemble PSC but have different causes and courses:

Secondary sclerosing cholangitis occurs when an identifiable underlying issue such as infection, gallstones, surgical complications, or physical injury leads to bile duct damage. In some cases, treating the underlying cause may improve the condition.

Pediatric primary sclerosing cholangitis develops in children or adolescents and may sometimes occur alongside autoimmune hepatitis, a condition in which the immune system attacks the liver.

Ascending cholangitis is an acute, potentially life-threatening infection of the bile ducts, most often triggered by a blockage such as a gallstone. It requires urgent medical treatment.

Researchers believe PSC is an immune-mediated disease, meaning the immune system mistakenly attacks the bile ducts. A related condition, primary biliary cholangitis, mainly affects the smaller bile ducts within the liver, occurs more commonly in women, and often responds to medication treatment.

Symptoms:

Common symptoms of PSC may include:

  • Persistent and extreme fatigue
  • Itching of the skin without a clear cause
  • Pain or discomfort in the upper right side of the abdomen
  • Diarrhea
  • Fever, often linked to repeated infections of the bile ducts
  • Yellowing of the skin or the whites of the eyes (jaundice), depending on skin tone

When to seek medical advice

Medical attention is recommended if there is unexplained, long-lasting itching over a large area of the body. It is also important to consult a healthcare professional if there is ongoing, severe tiredness that does not improve with rest.

People with inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease should be especially alert to persistent fatigue and discuss it with their doctor, as PSC is more common in these conditions.

Causes:

PSC is considered an immune-mediated disease, meaning the immune system mistakenly attacks healthy tissues in the body, particularly the bile ducts.

Inflammation is normally a protective response to injury or infection, increasing blood flow and activating immune defenses. While this process helps healing in the short term, long-term or misdirected inflammation can cause ongoing tissue damage.

In PSC, the exact trigger of bile duct inflammation is not fully understood. Research suggests the condition does not follow simple inheritance patterns from parents to children. Instead, it likely develops from a combination of genetic susceptibility and environmental influences.

Factors that may contribute include immune system dysfunction, changes in the gut environment such as alterations in the microbiome, and exposure to certain environmental triggers. A strong link exists between PSC and inflammatory bowel disease (IBD), particularly ulcerative colitis. Around 70% to 80% of people with PSC also have IBD, while a smaller proportion have Crohn’s disease.

Risk factors

Several factors may increase the likelihood of developing PSC:

  • Age: Can occur at any age but is most commonly diagnosed in middle adulthood
  • Sex: More frequently seen in males than females
  • Inflammatory bowel disease (IBD): About 5% to 7% of people with ulcerative colitis or Crohn’s disease also develop PSC
  • Geography: Higher rates have been reported in Northern Europe and North America
  • Genetics: Certain genetic variations may contribute to increased susceptibility

Complications

PSC can lead to several serious health complications, especially as the disease advances:

  • Liver disease and liver failure: Ongoing inflammation can cause scarring of the liver (cirrhosis), leading to a gradual loss of liver function
  • Cancer risk: Increased risk of bile duct and gallbladder cancers, along with a lower but still present risk of liver and pancreatic cancers. Those with both PSC and IBD also have a higher risk of colon and rectal cancer
  • Portal hypertension: Increased pressure in the portal vein can lead to blood vessel strain in the digestive system, internal bleeding, and fluid buildup in the abdomen
  • Bacterial infections: Blocked or narrowed bile ducts can become infected, especially after medical procedures
  • Bone weakness: Reduced bone density or osteoporosis may occur over time
  • Vitamin deficiencies: Impaired bile flow can affect absorption of vitamins A, D, E, and K, leading to deficiencies