Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B

J Gastroenterol. 2009;44(6):601-7. doi: 10.1007/s00535-009-0038-6. Epub 2009 Apr 22.

Abstract

Purpose: The antiviral effect of adefovir dipivoxil (ADV) added to ongoing lamivudine (LAM) treatment for LAM-resistant chronic hepatitis B (CHB) differs among patients. We investigated clinical factors affecting the response to ADV therapy in LAM-resistant CHB.

Methods: The subjects were 75 LAM-resistant CHB patients treated with ADV in addition to LAM. Virological response (VR) was defined as HBV DNA clearance (<2.6 logcopies/ml) at 12 months after the start of ADV therapy. Clinical factors contributing to VR were examined by univariate and multivariate analyses.

Results: Lower HBV DNA at baseline and negative hepatitis B e antigen (HBeAg) were significant factors affecting VR in univariate analysis. In multivariate analysis, lower HBV DNA at baseline (P = 0.005), negative HBeAg (P = 0.009), and higher ALT (P = 0.036) were significant independent factors contributing to VR. In HBeAg-positive patients, HBV DNA clearance was more frequently observed during ADV therapy in patients with baseline HBV DNA < or = 7.0 logcopies/ml than in those with baseline HBV DNA >7.0 logcopies/ml. By contrast, the link of lower HBV DNA at baseline to better therapeutic response was not evident in HBeAg-negative patients.

Conclusion: In ADV therapy added to ongoing LAM treatment for LAM-resistant CHB, lower baseline HBV DNA and negative HBeAg contributed to a better antiviral effect. Addition of ADV should be done promptly before marked increase in HBV DNA, especially in CHB patients showing LAM resistance positive for HBeAg.

Publication types

  • Multicenter Study

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / analysis
  • Drug Therapy, Combination
  • Female
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B e Antigens / analysis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / administration & dosage*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organophosphonates / therapeutic use*
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Organophosphonates
  • Lamivudine
  • Adenine
  • adefovir dipivoxil