Autoimmune liver disease

Regional differences in the manifestations of autoimmune hepatitis underscore the importance of genetic and/or environmental factors in its expression. The -308 polymorphism of TNF-A increases susceptibility to type 1 autoimmune hepatitis; HLA DRB1*13 is an important risk factor in South America; and DRB1*07 characterizes type 2 autoimmune hepatitis. Minocycline and mesalazine can trigger the disease, and interferon therapy can accentuate autoimmune manifestations. Autoimmune cholangitis in Japan is similar to primary biliary cirrhosis, and assays for carbonic anhydrase II lack diagnostic specificity. Perinuclear antineutrophil cytoplasmic antibodies are reactive to diverse nuclear antigens, but high mobility nonhistone chromosomal proteins may be important targets in autoimmune hepatitis. T cells can cross-react with viral and host peptides, and the candidacy of glutathione S-transferases as target autoantigens has been weakened. A murine model of PBC will be useful in studying mechanisms of autoreactivity, and cyclosporine has shown promise in the treatment of children with autoimmune hepatitis. Recurrence after liver transplantation is common, and it may require retransplantation. The human transplantation model will be valuable in understanding the host-and organ-specific contributions to disease expression.