4.5 Article

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

Journal

HEPATOLOGY RESEARCH
Volume 44, Issue 9, Pages 1000-1007

Publisher

WILEY
DOI: 10.1111/hepr.12284

Keywords

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

Funding

  1. National Basic Research Program of China (973 Program) [2011CB512106, 2013CB531501]
  2. State Key Project Specialized for Infectious Diseases [2011ZX09302-005]
  3. National Natural Science Foundation of China [81071694]
  4. TMMU [2012XLC05]

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AimThe reason why the majority of chronic hepatitis B (CHB) patients do not respond to conventional interferon (IFN)- 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- or PEG IFN therapy in Chinese patients with CHB. MethodsFour 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- 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 3log of baseline; and (iv) alanine aminotransferase normalization. ResultsBy 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- or PEG IFN treatment. ConclusionThis 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- or PEG IFN treatment.

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