Effect of HLA-DP and IL28B gene polymorphisms on response to interferon treatment in hepatitis B e-antigen seropositive chronic hepatitis B patients

Hepatol Res. 2014 Sep;44(9):1000-7. doi: 10.1111/hepr.12284. Epub 2014 Jan 9.

Abstract

Aim: The reason why the majority of chronic hepatitis B (CHB) patients do not respond to conventional interferon (IFN)-α or pegylated interferon (PEG IFN) treatment has not been formally demonstrated. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) and response to IFN-α or PEG IFN therapy in Chinese patients with CHB.

Methods: Four SNPs among the HLA-DPA1, HLA-DPB1 (rs3077 and rs9277535) and IL28B (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP genotyping assay in 144 hepatitis B e-antigen (HBeAg) seropositive CHB patients who had received 6-12 months IFN-α or PEG IFN treatment. Patients were classified as responders who achieved any of the four targets: (i) the loss of HBeAg; (ii) anti-HBe seroconversion; (iii) suppression of hepatitis B virus (HBV) DNA level to below 3 log of baseline; and (iv) alanine aminotransferase normalization.

Results: By multivariate analysis at 6 months of therapy and 6 months post-therapy, the results showed that rs3077-GG genotype was independently associated with higher HBeAg loss rate and anti-HBe seroconversion rate, and rs9277535-GG genotype was independently associated with decline of HBV DNA level. However, we did not observe the significant association between SNP near IL28B and the response to IFN-α or PEG IFN treatment.

Conclusion: This study suggested that HLA-DPA1 and HLA-DPB1 variants were significantly associated with HBeAg loss, anti-HBe seroconversion and HBV DNA level suppression in HBeAg seropositive CHB patients who received IFN-α or PEG IFN treatment.

Keywords: HLA-DP; IL28B; hepatitis B virus; interferon; single nucleotide polymorphisms.