Interferon for treatment of breakthrough infection with hepatitis B virus mutants developing during long-term lamivudine therapy

J Gastroenterol. 2002;37(11):922-7. doi: 10.1007/s005350200155.

Abstract

Background: We aimed to treat patients with chronic hepatitis B on long-term treatment with lamivudine who developed lamivudine-resistant hepatitis B virus (HBV) mutants along with clinical relapses.

Methods: Of 217 patients with chronic hepatitis B who had been treated with lamivudine for 1-6 years, 23 (11%) developed lamivudine-resistant hepatitis B virus (HBV) mutants. Seven of them, including 1 whose case was previously reported, received interferon (IFN) daily for 4 weeks and then two or three times a week thereafter to cope with exacerbation of hepatitis. We investigated the efficacy of this IFN therapy in 6 patients, excluding the 1 previously reported.

Results: In 4 patients, HBV DNA decreased to below the detectable limit of the branched DNA assay (<0.7 MEq/ml) accompanied by normalization of transaminase levels. During IFN therapy, 2 patients seroconverted to antibody to hepatitis B e antigen (HBeAg) and showed normalized transaminase levels. Interferon was required in 7 of the 111 (6%) patients with chronic hepatitis B who were positive for HBeAg, but in none of the 106 who were positive for antibody to HBeAg ( P = 0.014).

Conclusions: The efficacy of IFN in controlling virological breakthroughs and exacerbation of hepatitis by infection with lamivudine-resistant HBV mutants in patients with HBeAg-positive chronic hepatitis B could enhance the versatility of lamivudine, which may have to be given to them indefinitely.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Female
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Interferons / administration & dosage
  • Interferons / therapeutic use*
  • Lamivudine / administration & dosage
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Mutation / drug effects
  • Mutation / genetics*
  • Recurrence
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Interferons