68 - Primary and Secondary Sclerosing Cholangitis

Abstract

Sclerosing cholangitis encompasses a spectrum of cholestatic conditions that are characterized by patchy inflammation, fibrosis, and destruction of the intrahepatic and extrahepatic biliary tract. The most common and best described is PSC, which usually occurs in association with IBD, either UC or Crohn colitis. PSC may also be associated with a wide variety of fibrotic, autoimmune, and infiltrative disorders. PSC is an inflammatory disorder with a genetic basis similar to that for other autoimmune diseases. The underlying etiology and pathogenesis are not well understood but involve the direct link between gut and liver inflammation, likely mediated by immune cells, metabolites, bile acids, and/or microbes. Large-duct PSC occurs predominantly in men (male:female ratio 3:2) with IBD in 60% to 80% of cases and can progress to cirrhosis and cholangiocarcinoma. In the presence of IBD, patients with PSC also are at risk of colon cancer. Small-duct PSC refers to a group of patients who present with features compatible with PSC but lacks the typical cholangiographic findings of PSC. This condition is associated with a more favorable prognosis. No therapies other than LT can meaningfully alter the natural history of PSC. Many other causes of sclerosing cholangitis have been identified and, as a group, are referred to as secondary sclerosing cholangitis and include immunoglobulin G4-related sclerosing cholangitis, which typically occurs in older men and is highly responsive to glucocorticoids.