Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity. This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mononuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years. We propose to call this entity "anti-LKM1 chronic active hepatitis" or "autoimmune hepatitis type II" to differentiate it from classical "lupoid hepatitis" or autoimmune hepatitis type I.

We report a rare occurrence of systemic lupus erythematosus in a patient known to have had well-documented primary biliary cirrhosis for 10 years. The presentation was dramatic with pericardial tamponade, but responded well to high dose corticosteroid. There are only five such definite associations reported in the literature. In the present case, other possible causes were considered, such as drug-induced cholestasis, drug-induced lupus, autoimmune chronic active hepatitis and the overlap syndrome.

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)