Background & Aims
Genome‐wide association studies (GWAS) recently indicated that polymorphisms in the human leucocyte antigen (HLA)‐DP genes were associated with risk of persistent hepatitis B virus (HBV) infection and clearance of HBV, but the effect of HLA‐DP gene polymorphisms on the effect of antiviral therapy was unknown. We here investigated whether such polymorphisms were associated with decreases in HBsAg levels and seroclearance in patients who received long‐term lamivudine (LAM) treatment.
Methods
Japanese patients (202) who were hepatitis B e antigen positive at baseline, received LAM as first‐line treatment, and consented to HLA‐DP genotyping (HLA‐DPA1 rs3077 and HLA‐DPB1 rs9277535) were categorized into two cohorts, viz., a cohort who achieved virological response without rescue therapy (cohort 1) and those who did so with rescue therapy (cohort 2).
Results
Serum HBsAg levels declined significantly between year 3 and 9 from baseline among cohort 1 patients possessing ≥2 A‐alleles at rs3077 and rs9277535. The percentages of such patients in cohort 1 patients with decreases in HBsAg ≥0.5 log IU/ml were higher than those with <2 A‐alleles (71.8% [28/39] vs. 38.9% [23/59]; P = 0.004). However, there was no significant difference in cumulative HBsAg seroclearance rates between patients with ≥2 and those with <2 A‐alleles in cohort 1. In cohort 2, HBsAg seroclearance rates were higher in patients with ≥2 A‐alleles than in those with <2 A‐alleles (P = 0.003).
Conclusion
We found an association between HLA‐DP polymorphisms and decreases in HBsAg levels and seroclearance among HBeAg‐positive patients treated with LAM.