Gender and HLA type specific relapse rates in patients with autoimmune hepatitis
Aims: Autoimmune hepatitis (AIH) mostly affects women. The only available study on gender differences in risks to relapse reported a higher risk to relapse in men. However, this study did not reflect on the risk of multiple relapses. Furthermore, only little is known about seasonal contribution, e.g. by rate of viral infections, the role certain autoantibodies or HLA haplotypes in these gender differences, relapse rate, or prognosis.
Methods: We reviewed a large Northern Europe cohort of 306 Patients, 256 female and 50 male. For statistical analysis of the influence of gender and HLA haplotypes on relapse rates, zero-inflated poisson regression analysis was performed using data of 251 patients for which HLA type data were available.
Results: 41% of female and 46% of male patients suffered at least one relapse (p = 0.58). Analysis for seasonal influences on relapse rate did not identify relevant differences. Results of the zero inflated poisson model indicate that neither gender nor the HLA-Type influence the odds for staying relapse-free during follow-up. However, HLA DR4 positive patients had a statistically significant 41% higher relapse rate compared to DR4 negative patients (RR with 95%-CI = 1.41 [1.02 – 1.94]; p = 0.036). pANCA titer were associated with a clear trend towards a higher relapse rate without relevant gender differences. Although less obvious, increasing ANA, SMA, and LKM autoantibody titers may also be related to a higher number of relapses. Among these, increasing ANA antibodies and partially SLA antibody positivity may show gender specificity with an increased risk for women.
Conclusion: In patients at risk for multiple relapses of AIH, HLA DR4 positive patients carry a statistically significantly higher risk of multiple relapses and should therefore be closely monitored. The absolute number of relapses is similar across the seasons, indicating that a molecular mimicry of an increased seasonal viral infections risk is not obvious. The autoimmune diagnostics point towards several subgroups of gender specific and gender independent differences in relapse risk.