Management options for lamivudine-resistant chronic hepatitis B patients with suboptimal virological suppression by adefovir

Aliment Pharmacol Ther. 2011 Oct;34(8):972-81. doi: 10.1111/j.1365-2036.2011.04833.x. Epub 2011 Aug 24.

Abstract

Background: In chronic hepatitis B (CHB) patients, adefovir is commonly used as a rescue therapy for lamivudine resistance, but often results in incomplete virological suppression.

Aim: To study the factors predicting response to adefovir rescue, and the treatment response of tenofovir and entecavir in suboptimal responders to adefovir in CHB patients.

Methods: Chronic hepatitis B patients who took adefovir for at least 6 months for lamivudine resistance were studied. Early virological response was defined as undetectable HBV DNA at month 6. Maintained virological response was defined as undetectable HBV DNA till the last follow-up.

Results: Among 136 patients on adefovir for 39 (5-117) months, 30 (22%) had early virological response. The 3-year cumulative probability of maintained virological response was similar between patients on adefovir monotherapy (n = 53, 57.9%) and those on combination of lamivudine and adefovir treatment (n = 83, 56.5%). The month 6 HBV DNA was the only independent factor associated with maintained virological response (adjusted hazard ratio 0.49, 95% confidence interval 0.37-0.65, P < 0.001). Twenty-six of 30 (87%) early responders and 36 of 106 (34%) non-early responders had maintained virological response on adefovir (P < 0.001). Among 106 non-early responders, 18 and 11 were switched to tenofovir and entecavir, respectively. The 1-year cumulative probability of maintained virological response was higher in patients switched to tenofovir (87.5%) than those switched to entecavir (37.5%; P = 0.048) or continued with adefovir (8.7%; P < 0.001).

Conclusions: In adefovir rescue for lamivudine resistance, month 6 HBV DNA predicts maintained virological response in CHB patients. Switching to tenofovir achieved best viral suppression among suboptimal responders to adefovir.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / immunology
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use*
  • Cohort Studies
  • DNA, Viral / analysis
  • Drug Resistance, Viral / drug effects*
  • Female
  • Follow-Up Studies
  • Guanine / analogs & derivatives
  • Guanine / immunology
  • Guanine / therapeutic use
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / immunology
  • Organophosphonates / therapeutic use*
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Tenofovir
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Tenofovir
  • Adenine