Mutation in the S gene of hepatitis B virus and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in patients with chronic hepatitis B virus infection

J Med Virol. 2017 Aug;89(8):1419-1426. doi: 10.1002/jmv.24782. Epub 2017 Mar 14.

Abstract

The mechanism for the co-existence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in chronic HBV infected patients remains controversial. This study aimed to explore the role of HBV S gene mutation and anti-HBs subtype-nonspecificity in patients with simultaneous HBsAg/anti-HBs positivity. Chronic HBV infections with (n = 145, group I) and without (n = 141, group II) anti-HBs were included. The S gene was amplified and sequenced. The neutralization experiment was used in group I patients' sera to determine the specificity of anti-HBs. Additionally, the HBV vaccinated persons' sera were used to estimate the neutralize capacity of anti-HBs against HBsAg in group I patients. Results showed that 2.63% (145/5513) chronic HBV infected patients had positive results for anti-HBs. HBsAg amino acid (aa) substitution rate in 35 patients of group I was significantly higher than that in 58 patients of group II (1.89% vs 0.95%, P < 0.05), especially within "a" determinant (4.05% vs 1.22%, P < 0.05). In group I patients, anti-HBs in (74.29%, 26/35) patients was not directed to the subtypes of the co-existing HBsAg. Besides, some HBsAg variations in group I patients, sG145R mutation, inserted mutations, and continuous aa mutations within the major hydrophilic region (MHR), decreased the neutralized capacity of anti-HBs from HBV vaccinated persons. In conclusion, both of HBsAg mutation and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in chronic HBV infection. HBV vaccine recipients may still have a risk of HBV infection when exposure to patients with simultaneous HBsAg/anti-HBs positivity.

Keywords: antibodies to HBsAg; co-existence; hepatitis B surface antigen; mutation; serotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Mutant Proteins / blood
  • Mutant Proteins / genetics
  • Mutation*
  • Neutralization Tests
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA

Substances

  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Mutant Proteins