17-21 Because a higher maternal viral load leads to a higher likelihood of HBV breakthrough infection in infants,22-25 we hypothesized that the HBV genotype associated with a delayed clearance of HBeAg and a higher viral load would result in a higher rate of breakthrough infection. Thus the distribution of HBV genotypes may change in the immunization era. In this study, the secular trend of the HBV genotype distribution was investigated in Taiwanese
HBsAg-carrier children born before the implementation of the hepatitis B immunization program and in those born afterward. In addition, because perinatal transmission is an important route of HBV spread in Taiwan,3 HBV genotypes of HBsAg-positive mothers were also examined. Abbreviations: CI, confidence interval; 3-MA chemical structure HBeAg, hepatitis B e antigen; HBIG, MG-132 clinical trial hepatitis B immunoglobulin; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; PCR, polymerase chain reaction; SD, standard deviation; ULN, upper limit of normal. In Taiwan, the
hepatitis B immunization program beginning at birth was implemented on July 1, 1984. After the program was launched, hepatitis B serological tests were compulsory for all pregnant women so infants born to HBsAg-positive mothers could
be identified. Initially, the program covered only newborns of HBsAg-positive mothers; it was extended Amino acid to all newborns after July 1986. Before July 1992, four doses of a plasma-derived vaccine (Hevac B, Pasteur-Merieux, Lyon, France) or its equivalent (Lifeguard hepatitis B vaccine, Hsin-Chu, Taiwan) were given at 0, 1, 2, and 12 months of age. After July 1992, three doses of the recombinant vaccine H-B-Vax II (5 μg/0.5 mL; Merck Sharp & Dohme, Rahway, NJ) or Engerix-B (20 μg/mL; SmithKline Beecham, Rixensart, Belgium) were administered (within the first week of birth, at 1 month of age, and at 6 months of age). For newborns of HBeAg-positive mothers or HBsAg-positive mothers with a high titer of HBsAg (reciprocal titer >1:2560 as confirmed by reverse passive hemagglutination testing), 0.5 mL (100 IU) of hepatitis B immunoglobulin (HBIG) was administered within 24 hours of birth.10, 26 For newborns of HBsAg-positive but HBeAg-negative mothers, the administration of HBIG was optional. Four hundred seventy-one children who were 15 years of age or younger and had been diagnosed with chronic HBV infection (i.e., they were HBsAg-seropositive for at least 6 months) were recruited.