Rescue therapy for lamivudine-resistant chronic hepatitis B: comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy

J Gastroenterol Hepatol. 2010 Aug;25(8):1374-80. doi: 10.1111/j.1440-1746.2010.06381.x.

Abstract

Background and aim: There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add-on LAM combination therapy in LAM-refractory patients.

Methods: One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day).

Results: After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add-on therapy, respectively. A significantly higher log(10)HBV-DNA drop at 6 months occurred in the ADV add-on group compared with the ETV group. The rate of HBV-DNA polymerase chain reaction undetectability (<300 copies/mL) 6 months after initiation of ETV monotherapy, ADV monotherapy and ADV add-on therapy was 33.3%, 27.3% and 68.6%, respectively (P = 0.003). The cumulative HBeAg seroconversion rate was significantly higher in ADV add-on/ADV monotherapy groups compared with the ETV monotherapy group (P = 0.022). Viral breakthrough and genotypic resistance were detected in six (25.0%) and six (13.6%) patients in the ETV and ADV monotherapy groups, whereas no cases of genotypic resistance were detected in ADV add-on group 24 months after initiation of antiviral treatment (P < 0.01).

Conclusion: Adefovir add-on treatment in patients with LAM-resistant CHB suppresses HBV replication more effectively than ETV or ADV monotherapy. Additionally, no genotypic resistance was detected in the ADV add-on group.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Biomarkers / blood
  • DNA, Viral / blood
  • Drug Resistance, Viral* / genetics
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / administration & dosage*
  • Lamivudine / adverse effects
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage*
  • Organophosphonates / adverse effects
  • Republic of Korea
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Virus Replication / drug effects

Substances

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