[Effect of initial virologic response to adefovir on the development of resistance to adefovir in lamivudine-resistant chronic hepatitis B]

Korean J Hepatol. 2007 Sep;13(3):349-62. doi: 10.3350/kjhep.2007.13.3.349.
[Article in Korean]

Abstract

Background/aims: Adefovir dipivoxil (ADV) resistance in patients with lamivudine-resistant chronic hepatitis B is not well understood. This study examined the initial virologic response (IVR) to ADV, the rate of ADV resistance and the factors associated with ADV resistance.

Methods: Eighty one lamivudine-resistant HBeAg-positive patients were enrolled in this study. IVR was defined as HBV DNA < 4 log10 copies/mL after 6 months of therapy.

Results: IVR was observed in 37/81(45.7%) patients and it was associated with higher pretreatment ALT (P=0.002), and low pretreatment HBV DNA level (P=0.015). The HBV DNA levels were significantly higher in the non-IVR patients than the IVR patients at 12, 18 and 24 months (4.73 vs 2.59, 4.53 vs 2.31, 4.39 vs 2.40 log10 copies/mL, respectively; P<0.01). During the follow-up period, 17(21.0%) patients showed phenotypic resistance to ADV and 9 (11.1%) patients had ADV-resistant mutations. The cumulative probabilities of the phenotypic resistance to ADV at 12 and 24 months were 8.7% and 32.5%, respectively. The cumulative probabilities of the genotypic resistance to ADV at 12 and 24 months were 0% and 14.6%, respectively. Resistance to ADV was associated with a higher pretreatment HBV DNA (P=0.019), and non-IVR (P<0.001).

Conclusions: The cumulative probabilities of the phenotypic and genotypic resistance to ADV at 24 months were 32.5% and 14.6%. The high pretreatment HBV DNA and non-IVR (HBV DNA >/= 4 log10 copies/mL after 6 months of therapy) were associated with ADV resistance.

Publication types

  • English Abstract

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Drug Resistance, Viral
  • Female
  • Hepatitis B e Antigens / blood
  • 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 / therapeutic use*
  • Predictive Value of Tests
  • Retrospective Studies

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Lamivudine
  • adefovir
  • Alanine Transaminase
  • Adenine