[Hepatitis B in children: natural history and therapy]

Children with chronic hepatitis B, face life long disease and complications of cirrhosis and hepatocarcinoma. Naturally, it is estimated that half to two third of the children will clear the hepatitis Be antigen during childhood. Treatments aim to increase the HBe Ag to Ab seroconversion rate, which may also favour the loss of HBs antigen, ultimate goal. Interferon alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to increase the HBe ag loss from 11% in control group to 26% in treated patients (5 MU/square meter body surface area for six months) at one year, and 33% at 18 months. Side effects include mainly fever, flu like symptoms, and growth impairment during the treatment phase. Nucleotide analogues have now emerged as a promising alternative to treat chronic hepatitis B. The optimal dose for children is established to 3 mg/kg once daily up to 12 years old. Efficacy trials show complete virologic response in 23% of all treated patients after one year, as compared to 13% in the placebo group, and in 34% of patients with basal transaminases above two times upper limit of normal; versus 16% in controls. Lamivudine inhibits viral DNA which favours cellular immune response. Lamivudine resistance due to variant viruses is observed in 19% of children after one year. Other nucleotide analogues, such as entecavir and adefovir will soon be tested in children, and combination with Lamivudine may improve results. Finally, vaccine technology is being tested in adults, to induce a cellular immune response towards hepatitis B antigens, but no clinical benefit has so far been established.