Efficacy and safety of long-term adefovir dipivoxil therapy in children with
chronic hepatitis B infection.
Author(s): Jonas MM, Kelly D, Pollack H, Mizerski J, Sorbel J, Frederick D, Mondou E,
Rousseau F, Sokal E.
Affiliation(s): Division of Gastroenterology, Children's Hospital Boston, Boston, MA 02115, USA.
maureen.jonas@childrens.harvard.edu
Publication date & source: 2012, Pediatr Infect Dis J. , 31(6):578-82
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.
OBJECTIVES: 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.
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