Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B

OBJECTIVE: Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. METHODS: Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. RESULTS: Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. CONCLUSIONS: The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.