Interleukin-28 gene polymorphisms may contribute to HBsAg persistence and the development of HBeAg-negative chronic hepatitis B

Liver Int. 2015 Mar;35(3):846-53. doi: 10.1111/liv.12595. Epub 2014 Jun 10.

Abstract

Background & aims: Aim of this study was to investigate whether a potential association exists between several single nucleotide polymorphisms (SNPs) of the IL-28B gene (rs12979860, rs1188122, rs8099917, rs8105790, rs12980275) and HBsAg persistence. Further, a potential effect on the development of HBeAg-negative CHB vs. inactive HBsAg carrier state was assessed in a genotype D HBV cohort. A cohort of chronic HDV patients was also used to see if they behave differently compared to chronic HBV patients.

Methods: This study was conducted in three main patient cohorts: Group 1 consisted of 482 patients with HBsAg persistence. Of them 143 were inactive carriers, 94 had HBeAg-positive chronic hepatitis B (CHB) and 245 had anti-HBe-positive CHB. Group 2 represents spontaneously recovered HBV patients; they were anti-HBs and anti-HBc positive. Group 3 consisted of 176 chronic hepatitis delta (CHD) patients with antidelta and HDV-RNA positivity. DNA sequencing was performed for genotyping.

Results: When patients with HBsAg persistence were compared with spontaneously recovered patients, a significant difference was observed for rs8105790 (P < 0.0001), rs12980275 (P < 0.02). Patients who had the CC/TC genotype for rs8105790 (P < 0.0001) and AA genotype for 1188122 (P < 0.02) were more likely to be inactive HBsAg carriers, when inactive HBsAg carriers were compared with HBeAg-negative CHB patients. Comparison of CHD patients vs. recovered HBV patients was parallel to that of HBV persistence vs. recovered HBV with similar significant differences in same SNPs.

Conclusion: These results suggest that IL-28B polymorphisms may contribute to HBsAg persistence and the development of the inactive HBsAg carrier state.

Keywords: hepatitis B infection; hepatitis delta infection; interferon lambda 3; interleukin 28 B; single nucleotide polymorphisms.

MeSH terms

  • Adult
  • Carrier State
  • Cohort Studies
  • DNA, Viral / blood
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus
  • Hepatitis B, Chronic / genetics*
  • Hepatitis D, Chronic / genetics
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • interferon-lambda, human
  • Interleukins
  • Interferons