Significance and anamnestic response in isolated hepatitis B core antibody-positive individuals 18 years after neonatal hepatitis B virus vaccination in Taiwan

Vaccine. 2012 Jun 8;30(27):4034-9. doi: 10.1016/j.vaccine.2012.04.031. Epub 2012 Apr 22.


Aim: To investigate the significance of isolated hepatitis B core antibody (anti-HBc) and to analyze the response to hepatitis B virus (HBV) booster vaccination in young adults with isolated anti-HBc who had been fully vaccinated with HBV vaccine as infants.

Materials and methods: We screened 1734 new university entrants who had been fully vaccinated against HBV in infancy for the presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and anti-HBc upon university entry. Results positive for isolated anti-HBc were reconfirmed by testing for the presence of HBsAg and anti-HBc once more, and further evaluated for anti-HCV, anti-HIV, and HBV DNA status 6 months later. Students were also offered HBV booster vaccinations at that time. Geometric mean titers (GMT) of anti-HBs after one booster dose of HBV were compared between students with isolated anti-HBc and students with HBV naïve status.

Results: The overall prevalence of isolated anti-HBc in our student cohort was 1.2% (21 of 1734). No evidence of occult HBV infection was observed. A "booster" anamnestic response (anti-HBs titer ≥ 10 mIU/mL) was noted in 95% (20 of 21) of subjects with isolated anti-HBc. After re-measurement of anti-HBc, 13 (62%) of the 21 subjects with isolated anti-HBc were reclassified as having resolved HBV infection with a loss of anti-HBs. In the remaining 8 subjects (38%), isolated anti-HBc was determined to be false positive. The HBV status of these 8 subjects was HBV naïve due to the waning-off effect of anti-HBs of the neonatal HBV vaccination. There was no significant difference in anamnestic response to a single HBV booster dose of vaccine between students with isolated anti-HBc (n=13) and those with HBV naïve (n=323) status (GMT 50.6 vs 47.7 mIU/mL, P=0.90).

Conclusion: The presence of isolated anti-HBc 18 years after HBV vaccination can be attributed to post-HBV infection with a loss of anti-HBs and to a decline in anti-HBs elicited by vaccine. A single HBV booster dose of vaccine is recommended for subjects with isolated anti-HBc who were fully vaccinated with HBV vaccine as infants. This finding needs to be replicated in further studies with larger cohorts.

MeSH terms

  • Female
  • Hepatitis B / immunology
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunization, Secondary / methods
  • Immunologic Memory*
  • Infant
  • Infant, Newborn
  • Male
  • Taiwan
  • Vaccination / methods*
  • Young Adult


  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Vaccines