Universal infant immunization and occult hepatitis B virus infection in children and adolescents: A population-based study
Journal
Hepatology
Journal Volume
61
Journal Issue
4
Pages
1183-1191
Date Issued
2015
Author(s)
Abstract
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 104 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. ? 2014 by the American Association for the Study of Liver Diseases.
SDGs
Other Subjects
alanine aminotransferase; hepatitis B core antibody; hepatitis B surface antigen; hepatitis B vaccine; hepatitis B(e) antigen; hepatitis B core antigen; adolescent; age distribution; alanine aminotransferase blood level; Article; child; cohort analysis; controlled study; diagnostic test accuracy study; false positive result; female; gene mutation; genotype; hepatitis B; Hepatitis B virus; human; infant; male; mass immunization; microparticle enzyme immunoassay; mutation rate; nonhuman; nucleotide sequence; polymerase chain reaction; priority journal; promoter region; randomized controlled trial; school child; sensitivity and specificity; seroepidemiology; seroprevalence; sex ratio; virus infection; virus load; virus replication; wild type; blood; genetics; hepatitis B; immunization; Adolescent; Child; Female; Hepatitis B; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B virus; Humans; Immunization; Infant; Male
Publisher
John Wiley and Sons Inc.
Type
journal article