Rare Detection of Occult Hepatitis B Virus Infection in Children of Mothers with Positive Hepatitis B Surface Antigen

Abstract

The prevalence of occult Hepatitis B virus (HBV) infection in children was considerably varied from 0.1–64% in different reports. In this study we aimed to investigate the prevalence of occult HBV infection among the children born to mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China. Serum samples were collected from 210 children of 207 mothers with positive HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by nested PCR. Homology comparison of HBV sequences recovered from the child and mother was used to define the infection. Three children (1.43%) were positive for HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA positive by two nested PCR assays using primers derived from S and C genes. However, the sequence alignment showed that the sequences in each child were considerably different from those in his/her mother. Therefore, the sequences amplified from the children were very likely resultant from the cross-contaminations. Furthermore, the nine children with ‘positive HBV DNA’ were all negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti-HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV-infected mothers was found to have occult HBV infection. We conclude that the prevalence of occult HBV infection in vaccinated children born to HBsAg positive mothers should be extremely low. We recommend that homology comparison of sequences recovered from the child and mother be used to define the occult HBV infection in children born to HBV infected mothers.

Low occurrence of HBsAg but high frequency of transient occult HBV infection in vaccinated and HBIG‐administered infants born to HBsAg positive mothers

“…Comparing with previous studies, the prevalence of OBI babies born to HBsAg positive mothers was 42% in Indian babies age 6‐72 months, 28% in Iranian children age 10‐128 months, 0 or 4.9% in Chinese babies age 1‐51 months, respectively. Unfortunately, those studies did not compare babies OBI genotypes or sequences with their mothers.…”

“…3,4 The outcome of hepatitis B vaccination plus specific immune globulin (HBIG) in newborns to HBsAg positive mothers has been previously described. 5,6 In recent years, occult hepatitis B virus infection (OBI) was defined as the presence of HBV DNA in serum and/or liver but the absence of Ethical approval: This study was approved by the Medical Ethics Committee of Nanfang hospital of Southern Medical University, Guangzhou, China. All participant mothers signed an informed consent for themselves and babies.…”

“…The spots in black are index samples and those in grey are follow-up samples Analysis of three HBsAg+ babies and their mothers In order to investigate the potential causes of three apparent vaccination failures, the serological and DNA markers of HBV infections in paired infants and mothers were examined (SupplementaryTable S1). Mothers were all HBeAg+ with viral load ranging between 1.13 × 106 and 3.27 × 10 7 IU/mL quantified several months after delivery. Babies were anti-HBs negative (<1 mIU/mL), indicating non-response to HBV vaccination.…”

Occult hepatitis B virus infection, or occult cross‐contamination, in children of HBsAg‐positive mothers

“…2 In real-life practice, imperceptible cross-contamination may sometimes occur in performing PCR. 3 Therefore, the diagnosis of OBI should be ascertained before studying the natural history of OBI. Otherwise, the results would be misleading.…”

Be cautious for exceptional results in evaluating the effect of adolescent booster of hepatitis B vaccine

“…Whether these anti-HBc-positive children were also anti-HBs-positive is not known, as the authors did not mention this ; if positive, it should be nearly impossible to acquire a novel HBV infection except mutant virus. The authors used occult HBV infection (OBI) to explain the result (Shahmoradi et al, 2012), but OBI is extremely low in infants of HBsAg-positive mothers (Liu et al, 2014), and most of the reported OBI cases in vaccinated infants or children result from occult cross-contamination (Zhou, 2016). Actually, the same authors reported this high proportion of OBI in vaccinated children from the same area (Xu et al, 2010), but more than half of the OBI was caused by crosscontamination, as evidenced by 51.2% of isolates with an identical HBV sequence; this is impossible in different individuals except if they were infected with the same virus.…”