Pathogenesis of primary biliary cirrhosis

Autoimmune phenomena have been recognized in primary biliary cirrhosis (PBC) for more than 50 years and the specificity of the characteristic responses directed at highly conserved mitochondrial antigens determined in detail over the past 20. Effecter autoreactive immune responses are characterized and potential mechanisms of breakdown of tolerance to self proposed. Elements of the clinical pattern of PBC, including the recurrence of the disease across HLA boundaries after liver transplantation, remain difficult to reconcile with a simple autoimmune model. Alternative (but not necessary mutually exclusive) pathogenetic models have been outlined, including a potential role for retroviral pathogens and directly cytopathic effects.