Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy

J Hepatol. 2009 Apr;50(4):674-83. doi: 10.1016/j.jhep.2008.10.033. Epub 2008 Dec 29.

Abstract

Background/aims: We investigated the efficacy of entecavir in lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir treatment.

Methods: Fourteen chronic hepatitis B patients (57% lamivudine-experienced) with a viral load above 5log(10)copies/mL after 12months of adefovir therapy and thereafter were treated with entecavir 1mg daily.

Results: During a median follow-up of 15months (range: 8-23months) one of six lamivudine-naïve and none of the eight lamivudine-experienced patients achieved undetectable HBV DNA (<373copies/mL). HBeAg loss occurred in none of the subjects. Two lamivudine-experienced patients demonstrated the rtM204I mutation; no other entecavir-resistant substitutions were detected (rtI169, rtT184, rtS202, and rtM250). Two of three patients with genotypic adefovir resistance at baseline demonstrated a rapid virologic response to entecavir, but undetectable HBV DNA was not achieved. To attain a better antiviral response the dosage of entecavir was increased to 2mg daily in two patients, resulting in further viral load decline for both of them.

Conclusions: Entecavir monotherapy dosed at 1mg resulted in a slow reduction of viral load in both lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir therapy. Increasing the dosage of entecavir led to further HBV DNA decline.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood
  • DNA, Viral / drug effects
  • Female
  • Genotype
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • RNA, Viral / blood
  • RNA, Viral / drug effects
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • RNA, Viral
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine