Pathogenesis of autoimmune hepatitis

Autoimmune hepatitis (AIH) is an idiopathic disorder affecting the hepatic parenchyma. There are no morphological features that are pathognomonic of t he condition but the characteristic histological picture is that of an inte rface hepatitis without other changes that are more typical of other liver diseases. It is associated with hypergammaglobulinaemia, high titres of a w ide range of circulating auto-antibodies, often a family history of other d isorders that are thought to have an autoimmune basis, and a striking respo nse to immunosuppressive therapy. The pathogenetic mechanisms are not yet f ully understood but there is now considerable circumstantial evidence sugge sting that: (a) there is an underlying genetic predisposition to the diseas e; (b) this may relate to several defects in immunological control of autor eactivity, with consequent loss of self-tolerance to liver auto-antigens; ( c) it is likely that an initiating factor, such as a hepatotropic viral inf ection or an idiosyncratic reaction to a drug or other hepatotoxin, is requ ired to induce the disease in susceptible individuals; and, (d) the final e ffector mechanism of tissue damage probably involves auto-antibodies reacti ng with liver-specific antigens expressed on hepatocyte surfaces, rather th an direct T-cell cytotoxicity against hepatocytes. (C) 1999 Elsevier, Paris .