Autoimmune hepatitis: Half a century with a childhood disease

Autoimmune hepatitis (AIH) is a severe and unresolving inflammatory disease of the liver, of unknown etiology, carrying high morbidity and mortality. All ages and genders may be affected, with a peak incidence in prepubertal girls - although the disease has been diagnosed as early as age 6 months. AIH may be classified into two major subgroups according to the pattern of the autoantibody panel detected at diagnosis. AIH type 1 is characterized by the presence of anti-smooth muscle antibody (SMA) mostly with anti-actin specificity and/or by antinuclear antibody (ANA); AIH type 2 by anti-liver-kidney microsome antibody type 1 (LKM-1) and/or the anti-liver cytosol type 1 antibody (LC-1). The histological hallmark of AIH is "interface hepatitis", with a mononuclear cell infiltrate in the portal tracts, variable degrees of necrosis, and progressive fibrosis. The disease follows a chronic but fluctuating course usually progressing to cirrhosis and liver failure, even though the rapidity of progression is highly variable. AIH is thought to have a pathogenetic basis in an aberrant autoreactivity to hepatocyte antigens in genetically predisposed individuals. The most frequent onset is similar to that of an acute viral hepatitis with acute liver failure in some patients. About a third of patients have an insidious onset with progressive fatigue and intermittent jaundice while 10 to 15% are asymptomatic and are accidentally discovered by the finding of hepatomegaly and/or an increase in serum aminotransferase activity. Rarely AIH may manifest with the sings of portal hypertension such as bleeding from esophageal varices or by symptoms related to an associated autoimmune disorder. Corticosteroids alone or in conjunction with azathioprine are the treatment of choice inducing remission in over 90% of patients. Sustained response to therapy may result in substantial regression of fibrosis even in advanced cases. Rapid withdrawal of immunosuppression is associated with high risk of relapse. An alternative therapeutic strategy is cyclosporine. Liver transplantation manages patients with decompensated liver disease unresponsive to "rescue" medical treatment