Primary sclerosing cholangitis (PSC) is uncommon. In North America and Northern Europe its incidence is approximately 1–1.5 new cases per 100,000 population per year, and its prevalence is about 16 cases per 100,000. Most patients are between 25 and 45 years old, and the median age at diagnosis is about 41. About two-thirds of patients with PSC are men, and women with PSC are generally diagnosed at older ages than men.
The link with inflammatory bowel disease
The strongest association PSC carries is with inflammatory bowel disease (IBD), the chronic inflammation of the gut that includes ulcerative colitis and Crohn disease. Most patients with PSC also have IBD; reported proportions are commonly between 60% and 80%. The relationship runs mainly one way: only a small minority of patients with IBD develop PSC — about 2.4–4% of those with ulcerative colitis and about 1.4% of those with Crohn disease. An IBD clinic therefore sees PSC rarely, and, taking the association from the other side, every patient diagnosed with PSC needs to be assessed for bowel disease.
Genetic and immune risk factors
PSC is not inherited in a simple pattern, but genes contribute to susceptibility. A sibling of a patient with PSC has roughly an 11-fold higher risk of the disease than the general population, and certain human leukocyte antigen (HLA) types, the inherited proteins that present antigens to the immune system, are over-represented. About a quarter of patients have another autoimmune disease as well. These observations support the idea that PSC arises when a genetically susceptible person meets an environmental or immune trigger, rather than from a single cause.
Natural history and prognosis
PSC is usually progressive, but the rate varies greatly from one patient to another. The course is commonly divided into phases. In an asymptomatic phase, the cholangiogram shows bile-duct changes but the patient has no symptoms and the liver tests are normal. In a biochemical phase, the cholestatic liver tests become abnormal while the patient still feels well. In a symptomatic phase, fatigue, pruritus, jaundice and episodes of cholangitis appear. The disease may finally reach decompensated cirrhosis. The median time from diagnosis to death or liver transplantation is about 9 to 18 years, and within that wide range the pace of progression is what patients and clinicians plan around.