Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis.

Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB10301, DRB30101, DRB10401, and DRB40103, whereas the DRB11501 allele may protect from the disease. Our aim was to determine if these alleles or others influence clinical manifestations and prognosis. Eighty-six white patients were evaluated prospectively for immune features and outcomes. Class I alleles were determined by microlymphocytotoxicity, and class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes or sequence-specific primers. One hundred two white, normal subjects were typed in the same fashion. Patients with concurrent immunologic diseases were more commonly positive for DRB40103 than patients without these features (68% vs. 38%, P = .01). DRB10301 (86% vs. 45%, P = .008) and the DRB10301-DRB30101 haplotype (79% vs. 42%, P = .02) occurred more commonly in patients who deteriorated during corticosteroid therapy. In contrast, DRB10401 and the DRB10401-DRB40103 haplotype were associated with a lower frequency of death from liver failure or the need for transplantation than patients with other alleles (0% vs. 37%, P = .03). Patients with DRB10301 differed from those with DRB10401 in that they were younger and failed treatment more commonly (27% vs. 5%, P = .04). We conclude that alleles associated with susceptibility to type 1 autoimmune hepatitis also influence its clinical features and prognosis. DRB40103 is associated with concurrent immune diseases, DRB10301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation.