Chronologic changes in serum hepatitis B virus DNA, genotypes, surface antigen mutants and reverse transcriptase mutants during 25-year nationwide immunization in Taiwan.
We investigated breakthrough infection and hepatitis B virus (HBV) genetic changes in immunized subjects after 25 years of a universal infant immunization. Specifically, serum HBV DNA, genotypes, surface antigen mutants and nucleoside analog-resistant (NAr) mutants were assessed in 2853 subjects (<25 years old) surveyed in 2009, and these data were compared with the data from previous serosurveys. A comparison across different age-stratified groups using the 2009 data revealed a significant increase in the seropositive rate of anti-HBc (5.51% vs 12.38%, P=.001) and HBV DNA (1.13% vs 3.96%, P=.007) between those 17-22 and 23-24 years of age, possibly due to selective infant immunization in 1984-1986. Well-characterized NAr mutants, potential NAr mutants and surface "a" determinant mutants were detected in none, 15 (45.5%) and nine (27.3%) of 33 HBV DNA-positive subjects, respectively. Of 15 immunized, HBV DNA-positive young adults (18-24 years), three (20%) carried "a" determinant mutants. Amongst 1176 HBsAg-negative subjects evaluated for occult HBV infection, those seropositive for anti-HBc had a higher seropositive rate for HBV DNA (10/110, 9.1% vs 7/1066, 0.66%; P<.001) and "a" determinant mutants (4/110, 3.6% vs 0/1066; P<.001) than those seronegative for anti-HBc. Overall, the HBsAg-positive subjects in six serosurveys showed no significant increase in genotype C frequency in the comparison between the vaccinated and unvaccinated cohorts (25/98, 25.5% versus 14/79, 17.7%, P=.188). Over the 25-year programme, there was no increase in the prevalence of genotype C in HBsAg carriers and no increase in breakthrough HBV infection or surface mutant prevalence beyond adolescence. Nucleic acid amplification should still be considered the primary screening method for occult hepatitis B detection in high-risk recipients.
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan.
H-Y
HY
Hsu
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
M-H
0000-0002-3648-9261
MH
Chang
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Y-H
YH
Ni
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan.
C-L
CL
Chiang
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
J-F
JF
Wu
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan.
H-L
HL
Chen
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
P-J
PJ
Chen
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
D-S
DS
Chen
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D050505:Mutant Proteins / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D044967:Serum / Q000821:virology; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D050505:Mutant Proteins; D012194:RNA-Directed DNA Polymerase

HBV DNA
; genotype; nucleoside analog-resistant (NAr) mutants; occult HBV infection; surface antigen mutants; vaccination