Gender effects and synergisms with histocompatibility leukocyte antigens in type 1 autoimmune hepatitis.

Abstract

Our goals were to determine the effect of gender on the clinical features and treatment outcome of type 1 autoimmune hepatitis, and to assess synergisms with the known genetic risk factors. Clinical findings and treatment outcomes were compared in 144 women and 41 men who were also assessed for HLA DR3, HLA DR4, HLA DR3 and DR4 alleles, and the DRB1*1501-DQA1*102 haplotype by polymerase chain reaction. A total of 102 healthy men and women were similarly typed. Women were distinguished from men by higher frequencies of concurrent immune diseases (34% vs 17%, p = 0.05) and HLA DR4 (49% vs 24%, p = 0.007), as had been previously reported. Women, however, had a higher occurrence of non-DRB1*0401 DR4 alleles than men (15% vs 0%, p = 0.02), and men had a lower frequency of these alleles than did normal male subjects (0% vs 16%, p = 0.04). Men and women responded similarly to therapy. Treatment failure occurred more frequently in men only if they had HLA DR3 and women had HLA DR4 (25% vs 4%, p = 0.01). The DRB1*1501-DQA1*102 haplotype did not affect outcome. Gender influences susceptibility and clinical manifestations, but not outcome. Women have HLA DR4 more commonly than men, but this difference relates to their higher frequency of non-DRB1*0401 DR4 alleles. Female gender may promote risk associated with different HLA DR4 alleles.