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Universal infant immunization and occult hepatitis B virus infection in children and adolescents: a population-based
Hong-Yuan Hsu1, Mei-Hwei Chang, Yen-Hsuan Ni
1Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Primary Care Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Insights
Universal infant immunization significantly reduced occult hepatitis B virus (HBV) infection (OBI) in children. However, breakthrough infections in immunized individuals may increase OBI occurrence, highlighting the need for continued surveillance.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Universal infant immunization programs aim to prevent overt hepatitis B virus (HBV) infection.
- Occult HBV infection (OBI), characterized by detectable HBV DNA without hepatitis B surface antigen (HBsAg), poses a diagnostic challenge.
- The impact of infant immunization on OBI prevalence remains incompletely understood.
Purpose of the Study:
- To evaluate the effect of universal infant immunization on the frequency of occult hepatitis B virus (HBV) infection (OBI) in children.
- To compare OBI rates in vaccinated versus unvaccinated cohorts.
- To identify potential risk factors or markers for OBI in the post-vaccination era.
Main Methods:
- Analysis of serum samples from HBsAg-negative subjects under 18 years across six seroepidemiological surveys (1984-2009).
- Categorization of subjects into unvaccinated (born before 1984) and vaccinated (born after 1984) cohorts.
- Detection of HBV DNA using nested polymerase chain reaction (PCR) targeting multiple viral gene regions.
Main Results:
- OBI frequency was significantly lower in vaccinated than unvaccinated anti-HBc-negative subjects (0% vs. 1.8%).
- A trend towards higher OBI frequency was observed in vaccinated anti-HBc-positive subjects compared to unvaccinated counterparts (4.8% vs. 1.7%).
- Estimated OBI frequency per 10^4 HBsAg-negative subjects declined from 160.7 in unvaccinated to 11.5 in vaccinated cohorts.
Conclusions:
- Universal infant immunization effectively reduces OBI, complementing the reduction in overt HBV infections.
- Breakthrough HBV infections in immunized individuals may be associated with a higher incidence of OBI.
- Antibody to hepatitis B core antigen (anti-HBc) seropositivity serves as a valuable marker for OBI screening in HBsAg-negative, vaccinated individuals.
Unlabelled:
To determine whether universal infant immunization affects occult hepatitis B virus (HBV) infection (OBI), serum samples from hepatitis B surface antigen (HBsAg)-negative subjects <18 years enrolled during six sequential seroepidemiological surveys conducted between 1984 (just before universal infant immunization) and 2009 were analyzed. Study subjects were divided into unvaccinated cohorts (born before 1984) and vaccinated cohorts (born after 1984). HBV-DNA positivity was determined by positivity of nested polymerase chain reaction in at least two of three regions (pre-S, S, and pre-core/core genes). OBI frequency was lower in vaccinated than unvaccinated antibody to hepatitis B core antigen (anti-HBc)-negative subjects (0 of 392 [0%] vs. 4 of 218 [1.8%]; P = 0.007), tended to be higher in vaccinated than unvaccinated anti-HBc-positive subjects (16 of 334 [4.8%] vs. 3 of 181 [1.7%]; P = 0.072), and was higher in vaccinated than unvaccinated subjects seropositive for both antibody to hepatitis B surface antigen (anti-HBs) and anti-HBc (13 of 233 [5.6%] vs. 3 of 170 [1.8%]; P = 0.025). By using known anti-HBc seropositivity rate in children in our serosurveys, the estimated OBI frequency per 10(4) HBsAg-negative subjects declined from 160.7 in unvaccinated cohorts to 11.5 in vaccinated cohorts. In vaccinated cohorts, OBI frequency was higher in anti-HBc-positive subjects than in anti-HBc-negative subjects (16 of 334 [4.8%] vs. 0 of 392 [0%]; P < 0.001). Subjects with OBI had much lower viral load (P < 0.001) and a trend of higher mutation rates in "a" determinant of HBsAg than age-comparable, HBsAg-positive subjects.
Conclusions:
Reduction of OBI in immunized subjects complements the well-documented universal infant immunization-related benefit of markedly reduced overt HBV infection. Breakthrough infections in immunized subjects seem to associate with more occurrence of OBI than natural infections in unvaccinated subjects. In the postvaccination era, anti-HBc seropositivity is a useful marker for OBI screening in HBsAg-negative subjects, and a very-low-level viral replication and HBsAg expression is the major mechanism underlying OBI.
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