Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir

Clin Mol Hepatol. 2014 Sep;20(3):267-73. doi: 10.3350/cmh.2014.20.3.267. Epub 2014 Sep 25.

Abstract

Background/aims: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies.

Methods: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough.

Results: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001).

Conclusions: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

Keywords: Adefovir; Chronic hepatitis B; Entecavir; Lamivudine; Resistance.

MeSH terms

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

Substances

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