Abstract

ObjectiveOccult 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.MethodsA 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.ResultsAll 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).ConclusionsHBV 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.

Highlights

  • Occult hepatitis B virus (HBV) infection (OBI) is characterized by the persistence of HBV DNA in liver and/or serum without detectable hepatitis B virus surface antigen (HBsAg) [1]

  • 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

  • HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively

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Summary

Introduction

Occult hepatitis B virus (HBV) infection (OBI) is characterized by the persistence of HBV DNA in liver and/or serum without detectable hepatitis B virus surface antigen (HBsAg) [1]. The vast majority of the reported OBI-positive infants achieved protective levels of antibody to hepatitis B virus surface antigen (anti-HBs), without positivity for antibody to hepatitis B virus core antigen (anti-HBc). The maintenance of this cryptic condition remains elusive, mostly due to the lack of serial followups of OBI-positive infants from a prospective birth cohort in previous studies. To elucidate this perplexity, in this study, we prospectively followed up a birth cohort of immunized neonates born to HBsAg-positive mothers at 12, 24 and 36 months of age, after being diagnosed with OBI at 7 months of age, one month after the completion of primary HBV vaccination

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