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

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.