Relapse of hepatitis B in HBeAg-negative chronic hepatitis B patients who discontinued successful entecavir treatment: the case for continuous antiviral therapy

J Hepatol. 2009 Feb;50(2):289-95. doi: 10.1016/j.jhep.2008.10.017. Epub 2008 Nov 19.


Background/aims: To evaluate the off-treatment durability of response in HBeAg-negative chronic hepatitis B patients who achieved a protocol-defined 'Response' (HBV-DNA<0.7MEq/mL and ALT<1.25xULN) with entecavir at 48 weeks and the efficacy of entecavir in patients treated beyond one year.

Methods: Entecavir-treated and lamivudine-treated patients who achieved a protocol-defined 'Response' were evaluated off-treatment for HBV-DNA<300copies/mL and ALT normalisation. Entecavir- and lamivudine-treated patients who achieved a protocol-defined 'Virological Response' (HBV-DNA<0.7MEq/mL but ALT1.25xULN) at 48 weeks, continued blinded treatment until they achieved Response or 96 weeks, whichever came first.

Results: Among 'Responders' who discontinued treatment after 48 weeks, 7/257 (3%) entecavir-treated and 10/201 (5%) lamivudine-treated patients sustained HBV-DNA below 300copies/mL at 24-weeks off-treatment. Among the 54 patients who continued blinded treatment in the second year, 7/26 (27%) entecavir-treated and 6/28 (21%) lamivudine-treated patients normalised ALT and 22/26 (85%) entecavir-treated and 16/28 (57%) lamivudine-treated patients maintained HBV-DNA<300copies/mL at end-of-dosing. The safety profiles of both drugs remained comparable through a second year of treatment.

Conclusions: The majority of protocol-defined Responders relapsed after 1 year when treatment was discontinued. Treatment with entecavir beyond 1 year provided continued virological and biochemical benefit.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Double-Blind Method
  • Drug Resistance, Viral
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B e Antigens / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / therapeutic use
  • Recurrence
  • Viral Load


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Lamivudine
  • entecavir
  • Guanine
  • Alanine Transaminase