Autoimmunity in hepatitis

In trying to understand chronic hepatitis, it may be useful amid the confusion to distinguish between the etiology of the disease, the pathogenesis of the disease, and the secondary consequences of the disease. For example, a drug or a virus may be the etiologic agent of liver damage, the histology and auxiliary clinical manifestations may suggest an immunologic pathogenesis, and autoantibodies may be a secondary consequence. Drugs may certainly cause chronic hepatitis, and a strong case can be made for the hepatitis B virus (HBsAg), particularly when the disease evolves from an acute hepatitis. Wilson's disease is frequently accompanied by a chronic hepatitis, with or without the LE phenomenon, that resolves after penicillamine therapy. There is little evidence yet to suggest that an immunologic attack on the liver is a primary event in chronic hepatitis, but there is now some evidence that lymphocytes are specifically sensitized against liver components in chronic hepatitis. Furthermore, a number of clinical manifestations common in diseases of presumed immune pathogenesis occur in cases of chronic hepatitis of diverse etiology. Much of the case for an immunologic pathogenesis of chronic hepatitis, however, rests on evidence that seems more likely to reflect the secondary consequences of the disease: the antibodies described. These antibodies are all organelle antibodies. They have no clear relation to chronic hepatitis in terms of defining etiology or pathogenesis. Only mitochondrial antibody shows a consistent relation to a clinical syndrome. These antibodies may occur in cases of known etiology (drug, viral, and Wilson's disease) or of unknown etiology. In chronic hepatitis associated with a positive test for HBsAg, several of the antiorganelle antibodies may be found, and even the LE factor, though far less often than in cases of chronic hepatitis without HBsAg. Extrahepatic manifestations of autoimmune type and hyperglobulinemia may develop, but their incidence compared to the incidence in HBsAg negative cases has not been carefully studied. In this survey, the author first discusses the significance of autoantibodies classifying his subject as follows: lupus erythematosus cells and antinuclear antibody; antimitochondrial antibody; smooth muscle antibody and other autoantibodies. Subsequently, comment is given on extrahepatic manifestations; liver involvement in other autoimmune diseases; liver specific immunity and the immune system in liver diseases.