儿童HBV免疫接种

Yen-Hsuan Ni *. Department of Pediatrics， College of Medicine and Children’s Hospital， National Taiwan University， Taipei，Taiwan

The world’s first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July， 1984. Pregnant women were screened for serum HBsAg. Infants of highrisk mothers with positive HBeAg received HBIG within 24 h of birth in addition to vaccines. All infants received 3 doses (at 0， 1 and 6 months of age) of recombinant HBV vaccines. All of the vaccines and HBIG given to the infants were paid for by the government. HBV vaccination coverage rate is as high as 97% at present. Following the universal hepatitis B virus (HBV) vaccination program for infants in Taiwan 25 years ago， HBsAg sero-prevalence declined from about 10% to 0.6% in children under 15 years old in Taipei city during the past two decades. The sero-positive rates for HBsAg， anti-HBs， and anti-HBc were 1.2%， 50.5%， and 3.7%， respectively， in those born after the vaccination program (<20 years old) in 2004.

The institution of universal HBV vaccination decreases the incidence of HCC in children. From 1981 to 1994， the incidence of HCChepatocellular carcinoma in children 6 to 9 years of age declined from 0.52/100，000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001) in Taiwan. Later on， we extended the follow-up to 2000， the incidence of HCC per 100，000 children declined from 0.54 to 0.20 in those born before versus after the vaccination program. A positive maternal HBsAg status was found in 89% of the HBsAg sero-positive subjects born after the vaccination program.

In spite of the success of hepatitis B immunization， childhood HCC still failed to be completely eradicated by the universal vaccination program. This is evidenced by the very high HBsAg sero-positive rate in our HCC children (97%) and their mothers (96%).

The prevalence and clinical significance of the mutations in the a determinant (amino acids 121–149) of HBsAg was not well elucidated， particularly in the post-vaccination era. The prevalence of a determinant mutants in HBV-DNA positive children was 7.8% (8/103) in 1984， significantly increased to 19.6% (10/51) in 1989， peaked at 28.1% (9/32) in 1994， and remained at 23.1% (3/13) in 1999; it was higher in those fully vaccinated compared with those not vaccinated (15/46 vs. 15/153; p<，0.001). However， the number of mutant infected children in each survey was stable. The other group of subjects who are susceptible to vaccine failure is the immune- compromized hosts.

In conclusion， universal HBV vaccination provides long-term protection up to 20 years， and a universal booster is not indicated for the primary HBV vaccinees before adulthood. Mother-to-child transmission is the primary reason for vaccine failure and needs to be tackled in future vaccination programs. The emergence of escape mutant did not impose any increased risk of chronic infection at this moment. The development of new vaccines is expected to overcome the vaccine failure.