Sensitivity and accuracy of an updated line probe assay (HBV DR v.3) in detecting mutations associated with hepatitis B antiviral resistance

J Hepatol. 2009 Jan;50(1):42-8. doi: 10.1016/j.jhep.2008.08.020. Epub 2008 Nov 5.

Abstract

Background/aims: Early detection of antiviral drug-resistant mutations enables prompt initiation of rescue therapy. The aim of this study was to determine the accuracy and sensitivity of a new line probe assay in the detection of antiviral drug-resistant HBV mutations.

Methods: One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene.

Results: Complete concordance between line probe and sequencing results was observed for 90/121 samples (74.3%) and 1291/1331 amino acid positions (96.9%). Testing of follow-up samples and clonal analysis of discordant samples confirmed the presence of mutations where line probe assay but not direct sequencing detected mutations. HBV DR v.3 assay consistently detected mutations present in > or = 5% of the virus population when HBV DNA concentration was > or = 4 log10copies/mL.

Conclusions: The updated version of the line probe assay (HBV DR v.3) has high concordance with direct sequencing in detecting antiviral drug-resistant mutations but its sensitivity in detecting mutations at some positions needs to be improved.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use
  • DNA Probes / genetics
  • DNA Probes / standards*
  • DNA, Viral / genetics*
  • Drug Resistance, Viral / genetics*
  • Female
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B / drug therapy
  • Hepatitis B virus / genetics*
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Organophosphonates / therapeutic use
  • Sensitivity and Specificity

Substances

  • Antiviral Agents
  • DNA Probes
  • DNA, Viral
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine