title: Efficacy and safety of long-term adefovir dipivoxil therapy in children with chronic hepatitis B infection.
abstract: BACKGROUND
  The safety and efficacy of adefovir dipivoxil (ADV) for chronic hepatitis B infection in children was demonstrated in a randomized, placebo-controlled trial. Those children were followed for 4 more years, and many continued to receive ADV for all or part of this time.
  
  
  OBJECTIVE
  To examine the therapeutic effects and safety of prolonged ADV therapy in children with chronic hepatitis B infection.
  
  
  METHODS
  After 48 weeks of double-blind treatment, all placebo-treated subjects who did not exhibit HBeAg seroconversion at week 44, and all ADV-treated subjects, were offered open-label ADV for up to 192 additional weeks. Treatment was discontinued if there was no virologic effect, except for adolescents with previous lamivudine exposure, in whom lamivudine was added to ADV. Durability of HBeAg seroconversion was assessed. Annual resistance surveillance was conducted in subjects who had detectable hepatitis B virus DNA.
  
  
  RESULTS
  Of the 170 subjects who completed the 48-week study, 162 participated in the open-label study. ADV was discontinued in 61 subjects due to virologic failure. In subjects who continued treatment, either as monotherapy or with lamivudine, continued viral suppression and alanine aminotransferase normalization were noted. HBeAg seroconversions were observed in 55 subjects, and hepatitis B surface antigen seroconversion in 5. Mean duration of HBeAg seroconversion at last observation was 762 ± 371.2 days in the ADV-ADV group and 643 ± 291.5 days in the PLB-ADV group. ADV was safe and well-tolerated. Resistance to ADV was observed in 1 child on ADV monotherapy. Nine treatment-experienced subjects entered the study with mutations associated with lamivudine resistance. All responded to ADV therapy.
  
  
  CONCLUSIONS
  Prolonged ADV treatment is safe in children. If reserved only for those with virologic response within 6 months, viral resistance was minimal.
authors.affiliation: Division of Gastroenterology, Children's Hospital Boston, Boston, MA 02115, USA. maureen.jonas@childrens.harvard.edu
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.forename: Henry
authors.initials: H
authors.lastname: Pollack
authors.forename: Jacek
authors.initials: J
authors.lastname: Mizerski
authors.forename: Jeff
authors.initials: J
authors.lastname: Sorbel
authors.forename: David
authors.initials: D
authors.lastname: Frederick
authors.forename: Elsa
authors.initials: E
authors.lastname: Mondou
authors.forename: Franck
authors.initials: F
authors.lastname: Rousseau
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D006512:Hepatitis B Core Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D063065:Organophosphonates; D010919:Placebos; D000225:Adenine; C106812:adefovir dipivoxil