Variants of hepatitis B virus surface antigen observed during therapy with nucleic acid polymer REP 2139-Ca have no influence on treatment outcome and its detection by diagnostic assays

J Viral Hepat. 2019 Apr;26(4):485-495. doi: 10.1111/jvh.13044. Epub 2018 Dec 27.

Abstract

The treatment of patients suffering from HBeAg-positive chronic hepatitis B with REP 2139-Ca resulted in potent reductions in HBsAg and HBV DNA, seroconversion to anti-HBs and the establishment of functional control of infection. In this cohort of 12 patients, we investigated whether differences between HBsAg sequences might explain the lack of response to REP 2139-Ca observed in 3 of 12 patients. We also assessed if the reduction or complete loss of HBsAg in serum observed during therapy were caused by mutations in the "a" determinant preventing the detection of HBsAg by standard diagnostic assays. The complete pre-S/S open reading frame (ORF) was sequenced and pre-S1, pre-S2 and S amino acid sequences were analysed. We found no major differences between pre-S1, pre-S2 and S sequences in responders and nonresponders correlated with low reduction in HBsAg. In addition, we found no mutations in the "a" determinant that would significantly affect the reactivity of HBsAg in diagnostic assays. These results demonstrate that the amino acid sequence of complete pre-S/S ORF has no direct influence on response to REP 2139-Ca therapy.

Keywords: HBsAg; hepatitis B virus; mutation; nucleic acid polymer; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood
  • Genotype
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Mutation
  • Nucleic Acids / pharmacology*
  • Nucleic Acids / therapeutic use*
  • Polymers / pharmacology*
  • Polymers / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Nucleic Acids
  • Polymers
  • REP 2139