Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon

Pediatr Infect Dis J. 2003 Mar;22(3):224-9. doi: 10.1097/01.inf.0000055062.64965.2e.

Abstract

Background/aims: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. This prospective open study reports the results of lamivudine treatment in children with chronic hepatitis B infection who did not respond to previous interferon treatment.

Patients and methods: Lamivudine, 3 mg/kg/day (maximum, 100 mg/day), was given for 52 weeks to 20 children and adolescents, ages 8.5 to 19 years, with chronic hepatitis B infection who had been treated with interferon 2 to 5 years earlier. We evaluated virologic and biochemical responses, the occurrence of YMDD mutants and adverse effects.

Results: All children were HBV DNA+, hepatitis B e antigen (HBeAg) /anti-hepatitis B e antibody- at start of treatment. At the end of 1 year, HBV DNA declined by 95% in all patients, and 8 of 18 (44%) had sustained undetectable HBV DNA by hybridization assay. Median pretreatment alanine aminotransferase (ALT) x1.5 upper limit of normal decreased to ALT x0.9 upper limit of normal after 1 year. One child became HBeAg-negative. YMDD mutants were detected in 11 of 17 (65%) children after 1 year of lamivudine treatment. Among children with YMDD mutant variants, 54% maintained normal ALT values and 45% had undetectable HBV DNA by hybridization assay. No adverse effects were observed.

Conclusions: Children with chronic hepatitis B infection treated with lamivudine after failure of interferon therapy had decreased HBV replication and improved ALT values. However, lamivudine treatment resulted in an exceptionally high rate of lamivudine-resistant mutants and low HBeAg seroconversion rate.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Chi-Square Distribution
  • Child
  • DNA, Viral / analysis*
  • DNA, Viral / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B Surface Antigens / drug effects
  • Hepatitis B virus / drug effects*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Interferons / administration & dosage
  • Lamivudine / administration & dosage*
  • Lamivudine / adverse effects
  • Liver Function Tests
  • Male
  • Prognosis
  • Prospective Studies
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / adverse effects
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome

Substances

  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Interferons