Chronologic changes in serum hepatitis B virus DNA , genotypes, surface antigen mutants and reverse transcriptase mutants during 25‐year nationwide immunization in Taiwan

Summary 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 ( NA r) 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‐ HB c (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 NA r mutants, potential NA r 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 HB sAg‐negative subjects evaluated for occult HBV infection, those seropositive for anti‐ HB c 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‐ HB c. Overall, the HB sAg‐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 HB sAg 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.