Pediatrics, University of California, San Francisco, CA, United States.
The Hospital for Sick Children, and Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
Pediatrics, University of Washington School of Medicineand Seattle Children's Hospital, Seattle, WA, United States.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States.
Pediatrics, Saint Louis University, Saint Louis, MO, United States.
Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
The optimal management strategy for children with immune-tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune-tolerant phase of HBV infection. Children with immune-tolerant features of chronic hepatitis B received entecavir once daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa-2a (180 μg/1.73m2subcutaneously) once weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable HBeAg with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range 3.4-17.9) years, were enrolled. All were positive for HBsAg and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty-five children completed the entire 48-week course of therapy. At 48 weeks after treatment ended (week 96), two children (3%) achieved the primary endpoint and were also HBsAg negative and anti-HBs positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72 which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty-seven children experienced adverse events (AE) and one had a serious AE.
The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune-tolerant phase of HBV infection, and treatment was associated with frequent AEs.