Serological and molecular response on combined antiviral treatment in children with chronic hepatitis B after pediatric malignancy.
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.
Lackner
Herwig
H
Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescence Medicine, University Hospital, A-8036 Graz, Austria. herwig.lackner@uni-graz.at
Moser
Andrea
A
Benesch
Martin
M
Deutsch
Johann
J
Kessler
Harald H
HH
Kerbl
Reinhold
R
Schwinger
Wolfgang
W
Dornbusch
Hans Jürgen
HJ
Sovinz
Petra
P
Urban
Christian
C
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
D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015075:2-Aminopurine; D000077595:Famciclovir; D011241:Prednisone