Pathogenesis of Sclerosing Cholangitis: The Role of Nonimmune Factors

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Abstract
The diagnosis of primary sclerosing cholangitis is made on cholangiographic appearances supported by liver histologic findings. Clinical features may be compatible but are not diagnostic and there is no specific diagnostic test. Immunologic mechanisms have been proposed as pathogenetic, but the evidence is far from conclusive. Similar cholangiographic and histologic changes are found in other diseases of known etiology, including infections with intestinal bacterial organisms and with cryptosporidiosis. Primary sclerosing cholangitis has a strong association with ulcerative colitis and possible mechanisms are discussed. Gut-derived toxic bacterial products may be implicated in the biliary damage. Vascular damage to the hepatic arterial tree by cytotoxic drugs, or after hepatic transplantation, also may produce the picture of sclerosing cholangitis. If the syndrome of sclerosing cholangitis can have so many possible causes, it seems likely that the "primary" type eventually may be found to have a known etiology (possibly infectious). At that point, it will no longer be considered primary.

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