Add-on adefovir is superior to a switch to entecavir as rescue therapy for Lamivudine-resistant chronic hepatitis B

Dig Dis Sci. 2011 Jul;56(7):2130-6. doi: 10.1007/s10620-010-1561-2. Epub 2011 Jan 21.

Abstract

Background/aims: Lamivudine (LAM) has been extensively used to treat hepatitis B, but high incidence of drug resistance has required rescue studies. We validated the optimum treatment strategy for LAM-resistant patients by means of a comparative study of add-on adefovir (ADV) and a switch to entecavir (ETV).

Methods: We assessed the virologic response in consecutive LAM-resistant patients who received add-on ADV or a switch to ETV.

Results: The mean reduction of serum hepatitis B virus (HBV) DNA levels was significantly less in the ETV group than in the add-on ADV group (-3.45 vs. -4.17; P = 0.047 at week 24 and -3.81 vs. -4.68 log(10) IU/mL; P = 0.044 at week 48). Achievement of undetectable HBV DNA was significantly lower in the ETV group than in the add-on ADV group (P = 0.043). Multivariate analysis showed that add-on ADV, baseline HBV DNA levels, and initial virologic response were significant predictors of HBV DNA negativity (adjusted OR, 2.582; P = 0.008, 0.304; P = 0.001, and 5.928; P = 0.001). Virologic breakthrough was observed for 12 patients, in the ETV group only.

Conclusions: Add-on ADV was more effective and durable than ETV as rescue therapy. Therefore, add-on ADV might be the preferred strategy for LAM-resistant patients who need long-term antiviral treatment.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine