title: Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Pediatric Gastroenterology and Nutrition, Meyer Children's Hospital of Haifa, Israel.
authors.forename: Corina
authors.initials: C
authors.lastname: Hartman
authors.forename: Drora
authors.initials: D
authors.lastname: Berkowitz
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Orly
authors.initials: O
authors.lastname: Eshach-Adiv
authors.forename: Bian
authors.initials: B
authors.lastname: Hino
authors.forename: Nurit
authors.initials: N
authors.lastname: Rimon
authors.forename: Iehudith
authors.initials: I
authors.lastname: Satinger
authors.forename: Tzipi
authors.initials: T
authors.lastname: Kra-Oz
authors.forename: Nily
authors.initials: N
authors.lastname: Daudi
authors.forename: Raanan
authors.initials: R
authors.lastname: Shamir
mesh_terms: D000293:Adolescent; D016009:Chi-Square Distribution; D002648:Child; D004279:DNA, Viral / Q000032:analysis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008111:Liver Function Tests; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D007372:Interferons