Environmental factors in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease more commonly found in women (with most cases being diagnosed in the fourth to fifth decades of life) that share peculiar features. Among these, serum antimitochondrial autoantibodies (AMA), serum hyper-immunoglobulin M, and progressive destruction of intrahepatic bile ducts are the most common clinical findings. The pathogenesis of the selective destruction of small-duct biliary epithelial cells is still unknown, although an autoimmune mechanism appears likely due to the detection of autoreactive T and B cells. Genetic background is critical in determining susceptibility to the disease, despite the limited associations with alleles within the major histocompatibility complex. However, among other observations, incomplete concordance of the disease in monozygotic twins and epidemiology strongly support a role for environmental factors in PBC onset. Molecular mimicry by either infectious agents or chemicals has been proposed to induce breakdown of immune tolerance in genetically predisposed individuals. This hypothesis is further supported by clinical (risk factors) and experimental evidence obtained also in animal models.