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. 2016 Nov 11;11(11):e0166317.
doi: 10.1371/journal.pone.0166317. eCollection 2016.

Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study

Ying Lu  1 , Ya-Lin Liu  1 , Jing-Jing Nie  1 , Xiao-Feng Liang  2 , Ling Yan  1 , Fu-Zhen Wang  2 , Xiang-Jun Zhai  3 , Jian-Xun Liu  4 , Feng-Cai Zhu  3 , Zhan-Jun Chang  4 , Jie Li  1
Affiliations

Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study

Ying Lu et al. PLoS One. .

Abstract

Objective: Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort.

Methods: A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5.

Results: All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20-3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003).

Conclusions: HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Phylogenetic trees of mother-child HBV pairs.
(A) phylogenetic tree of RT region; (B) phylogenetic tree of Pre-S region; (C) phylogenetic tree of Core region.
Fig 2
Fig 2. The occurrence of OBI stratified by maternal HBV DNA levels and HBsAg titers.
(A) stratified by HBV DNA levels; (B) stratified by HBsAg titers.
See this image and copyright information in PMC

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