Hepatitis B virus mutation in children.

Due to the lack of proof reading activity of hepatitis B virus (HBV) polymerase, mutation/variation of the viral sequence is frequently found during long term follow-ups. In the majority of children with chronic HBV infection, wild type HBV is the dominant viral strain during the natural course of chronic HBV infection. During long-term follow-up, HBV precore mutants developed spontaneously in approximately 10 to 24% of children before HBeAg seroconversion and in around 50% of children after HBeAg seroconversion mutants. Occasionally, children may be infected primarily by mutant strains of HBV. Approximately 36% of children with fulminant hepatitis and 30% of children with acute hepatitis B were infected by precore mutants of HBV transmitted by their mothers or blood donors. In addition, after universal HBV vaccination, HBV surface gene variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. In HBV DNA positive children from four sequential surveys in Taiwan, the prevalence of hepatitis B surface gene a determinant mutants increased from 7.8% before the vaccination program, to 19.6%, 28.1% and 23.1% at 5, 10 and 15 years after the program. Nucleoside analogue may also induce mutant strains, which reduces the antiviral effects. The most common example is the YMDD mutation of the HBV polymerase gene after antiviral therapy with lamivudine. It developed in 19% of the treated children. In conclusion, children may be infected primarily by mutant strains of HBV either naturally during acute HBV infection. Those infected with wild type HBV initially may develop mutant strains gradually during the course of chronic infection under the host immune pressure. Vaccine escape mutants may develop after immunoprophylaxis. In addition, antiviral therapy with nucleoside analogues may also induce drug resistant mutant strains. Understanding the viral mutation status will help to design accurate strategies of immmunoprophylaxis and antiviral therapy against HBV infection.