Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine-resistant mutants of hepatitis B virus

Intervirology. 2004;47(6):362-9. doi: 10.1159/000080881.

Abstract

Objective: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants.

Methods: Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis.

Results: At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and -22.3 times the ULN in the ADV + IFN group.

Conclusions: Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use*
  • Adult
  • Alanine Transaminase / blood
  • Drug Resistance, Microbial / genetics
  • Female
  • Genotype
  • Hepatitis B / drug therapy*
  • Hepatitis B / virology
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / physiology
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use
  • Lamivudine / pharmacology*
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Safety
  • Treatment Outcome

Substances

  • Interferon-alpha
  • Organophosphonates
  • Lamivudine
  • Alanine Transaminase
  • Adenine
  • adefovir dipivoxil