Antiviral drug resistance testing in patients with chronic hepatitis B

Dig Dis Sci. 2012 Jan;57(1):221-31. doi: 10.1007/s10620-011-1816-6. Epub 2011 Jul 9.

Abstract

Background: Antiviral drugs against hepatitis B virus are limited by the emergence of drug resistance.

Aims: We aimed to study the impact of drug resistance testing on treatment decisions.

Methods: In part 1 of this study, consecutive patients with chronic hepatitis B who had antiviral drug resistance testing were studied. Part 2 was a two-step questionnaire survey including ten characteristic case scenarios. Hepatologists were asked about their treatment decisions before and after the knowledge of drug resistance results.

Results: Fifty-one patients underwent drug resistance testing, most of whom were on lamivudine, adefovir dipivoxil or entecavir monotherapy. Thirty-four (67%) patients had drug-resistant mutants detected, 4 (8%) had low viral load, and 13 (25%) harboured wild-type virus. Twenty-nine of 34 (85%) patients harbouring drug-resistant mutants and 9 of 17 (53%) patients with no mutants detected changed their drug regimens (P = 0.038). In part 2, 18 hepatologists completed all two questionnaires. Overall, treatment decision was modified in 52% of cases upon receiving the drug resistance testing results. The detection of rtA181V/I resulted in decision changes in most hepatologists, with the preferred treatment switching from tenofovir to entecavir. When no mutants were detected in partial responders to entecavir monotherapy, most hepatologists chose to increase the dose of entecavir.

Conclusions: Drug-resistant mutations are detected in around two-thirds of chronic hepatitis B patients undergoing drug resistance testing. Drug resistance testing alters management in over half of the cases, and should be considered in all patients with virological breakthrough and suboptimal virological suppression.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Data Collection
  • Decision Making
  • Drug Resistance, Viral / genetics*
  • Female
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Organophosphonates / therapeutic use
  • Retrospective Studies
  • Surveys and Questionnaires
  • Tenofovir
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • entecavir
  • Guanine
  • Tenofovir
  • Adenine