Diagnosis, Differential Diagnosis, and Epidemiology of Primary Sclerosing Cholangitis

According to recent guidelines, primary sclerosing cholangitis (PSC) is diagnosed when a patient has a cholestatic liver enzyme profile, characteristic bile duct changes on imaging, and when secondary causes of sclerosing cholangitis are excluded. In patients with a clinical suspicion but normal cholangiography, a liver biopsy is indicated to establish a diagnosis of small duct PSC. Several other disease entities such as IgG4-associated cholangitis (IAC), cholangiocarcinoma (CCA), and secondary causes of sclerosing cholangitis such as choledocholithiasis, AIDS-cholangiopathy, ischemia, surgical bile duct trauma, or mast cell cholangiopathy can mimic PSC. IAC can be differentiated from PSC by applying the HISORt criteria including the serum IgG4 level. In cases where serum IgG4 is less than 2 × ULN, the ratio of IgG4/IgG1 >0.24 is indicative for IAC. Choledocholithiasis with recurrent cholangitis as a cause of sclerosing cholangitis can pose a conundrum, since PSC itself is associated with an increased prevalence of gallstones. The epidemiology of PSC worldwide has been poorly described. Incidence and prevalence rates vary from 0-1.3 and 0-16.2 per 100,000 inhabitants respectively. However, these figures are not based on population-based cohorts. A recent large population-based cohort from the Netherlands reported an incidence of 0.5 and a prevalence of 6/100,000. Approximately 10% fulfil the criteria for small duct PSC. At diagnosis of PSC, concurrent inflammatory bowel disease (IBD), primarily ulcerative colitis or Crohn's colitis is present in 50%, but increasing to 80%, 10 years or more after diagnosis. Conversely, 3% of IBD patients will develop PSC. PSC predisposes to malignancy. The estimated cumulative risk of developing CCA after 30 years is 20%. For colorectal carcinoma in PSC/colitis patients, the estimated cumulative risk at 30 years is 13%.