Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation

J Hepatol. 2005 Dec;43(6):937-43. doi: 10.1016/j.jhep.2005.05.037. Epub 2005 Jul 7.


Background/aims: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection.

Methods: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene.

Results: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients.

Conclusions: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Disease Progression
  • Drug Resistance, Viral / genetics*
  • Hepatitis B / drug therapy*
  • Hepatitis B / virology
  • Hepatitis B virus / genetics*
  • Humans
  • Liver Failure / etiology
  • Liver Failure / virology
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Viral Load


  • Antiviral Agents
  • Organophosphonates
  • adefovir
  • Adenine