Drug treatment of pediatric chronic hepatitis B

Children with chronic hepatitis B are at risk of developing long-term complications such as cirrhosis and hepatocarcinoma. It is estimated that half to two-thirds of affected children will clear the hepatitis B e antigen (HBeAg) naturally before reaching adulthood. As in adults, treatments in children accelerate the virological response (DNA negativity and HBeAg loss, with anti-HBe seroconversion), which is associated with normalization of transaminase levels. Treatments also favor subsequent loss of hepatitis B surface antigen (HbsAg), the ultimate goal for minimizing long-term consequences. Interferon-alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to promote DNA negativity and HBeAg loss in 26% of treated patients (6 MU/m(2) body surface area for 6 months) at 1 year and 33% at 18 months (versus 11% in controls). 10% of treated patients also lost HBsAg. Adverse effects mainly included fever, flu-like symptoms and growth impairment during the treatment phase. Nucleotide analogs have now emerged as promising alternatives for the treatment of chronic hepatitis B. Lamivudine dose-ranging studies showed a higher clearance in children, and the optimal dosage was established to be 3 mg/kg once daily in children up to 12 years of age. Efficacy trials showed complete virological response (HBeAg loss and DNA negativity) in 23% of all treated patients after 1 year, and in 34% of patients with initial transaminase levels >2 x the upper limit of normal. Lamivudine resistance due to mutant/variant viruses is observed in 19% of children after 1 year, a figure that may increase by an average of 20% per year. Other nucleotide analogs, such as adefovir, will soon be tested in children, and have shown promising results in adults without so far demonstrating viral resistance. Finally, therapeutic vaccines aiming to induce a cellular immune response towards hepatitis B antigens are being tested in adults, but no clinical benefit has so far been established.