Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: A second type of “autoimmune” hepatitis

Abstract

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.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis

“…Allele and genotype frequencies were compared using 2 and Fisher exact tests, as appropriate. All analyses were performed on a personal computer using the Epistat statistical software (Epi-info; CDC, Atlanta, GA).…”

“…Type 2 AIH is characterized by antibodies to liver-kidney microsome type 1 (anti-LKM1) and occurs mainly in children. 2,3 Genetic factors contribute to susceptibility for most autoimmune diseases, including Graves' disease, myasthenia gravis, multiple sclerosis, primary Sjö gren' s syndrome, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and rheumatoid arthritis. 4 In type 1 AIH, genetic involvement is indicated by a marked female preponderance and strong, well-established, human leukocyte antigen (HLA) associations.…”

Successful tacrolimus therapy for a severe recurrence of type 1 autoimmune hepatitis in a liver graft recipient

“…Liver biopsy showed chronic hepatitis, with a METAVIR score of A2F2. 6 She was administered interferon (Introna; Schering Plough, Kenilworth, NJ), 3 million units, 3 times weekly from February to September 1992, which induced an incomplete biochemical response with persistent HCV viremia. ASMA titers were not measured during interferon therapy.…”

Cytochrome P4502D6193–212: A New Immunodominant Epitope and Target of Virus/Self Cross-Reactivity in Liver Kidney Microsomal Autoantibody Type 1-Positive Liver Disease

“…L iver kidney microsomal Ab type 1 (LKM1) 3 is the diagnostic marker of autoimmune hepatitis type 2 (AIH2), AIH1 being characterized by the presence of antinuclear Ab and/or smooth muscle Ab (1). LKM1 is also present in up to 10% of patients with chronic hepatitis C virus (HCV) infection, where it appears to confer severity to the disease process, as shown by Giostra et al (2), and to predispose to adverse reactions during treatment with IFN (3).…”