title: Serological and molecular response on combined antiviral treatment in children with chronic hepatitis B after pediatric malignancy.
abstract: BACKGROUND
  Chronic hepatitis B is a serious long-term problem for children surviving malignancy. The annual rate of spontaneous clearance of hepatitis B e antigen (HBeAg) is only 3% in these patients, and the response to monotherapy with interferon (IFN)-alpha is also low.
  
  
  OBJECTIVE
  To monitor the serological and molecular response on combined antiviral treatment in children with chronic hepatitis B after pediatric malignancy.
  
  
  METHODS
  Twelve patients with a history of childhood malignancy and chronic hepatitis B were treated with prednisone for 4 weeks (0.6 mg/kg body weight per day orally for 3 weeks followed by 0.3 mg/kg body weight per day for 1 week) followed by IFN-alpha-2a (5 megaunits/m(2) body surface area, three times a week, subcutaneously) at least for 1 year. After 1 year of IFN-alpha monotherapy, treatment was discontinued in patients with HBeAg seroconversion as well as patients without HBeAg seroconversion and a decrease of serum hepatitis B virus (HBV) DNA level less than 0.5 logs of the basal level. Patients who had a decrease of the serum HBV DNA of more than 0.5 logs of the basal level underwent treatment continuation with IFN-alpha combined with famciclovir (FAM) (20 mg/kg body weight per day orally) for another year.
  
  
  RESULTS
  After 1 year of IFN-alpha monotherapy, a decrease of the serum HBV DNA level to less than 0.5 logs was found in eight of 12 patients. Two of them additionally developed HBeAg seroconversion after 3 and 12 months. The remaining six patients received antiviral treatment with IFN-alpha combined with FAM for another year. Two of them showed HBeAg seroconversion after 21 and 24 months from study entry. HBeAg seroconversion was only observed in patients who had a decrease of serum HBV DNA to levels below 1 x 10(6) copies/ml. Treatment-induced toxicity was moderate and reversible in all patients.
  
  
  CONCLUSIONS
  Combination treatment of chronic hepatitis B with prednisone, IFN-alpha, and FAM seems to be a safe and effective treatment option for children surviving pediatric malignancy.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescence Medicine, University Hospital, A-8036 Graz, Austria. herwig.lackner@uni-graz.at
authors.forename: Herwig
authors.initials: H
authors.lastname: Lackner
authors.forename: Andrea
authors.initials: A
authors.lastname: Moser
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Johann
authors.initials: J
authors.lastname: Deutsch
authors.forename: Harald H
authors.initials: HH
authors.lastname: Kessler
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kerbl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Dornbusch
authors.forename: Petra
authors.initials: P
authors.lastname: Sovinz
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D000077595:Famciclovir; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012449:Safety; D012703:Serotyping; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015075:2-Aminopurine; D000077595:Famciclovir; D011241:Prednisone