Clearance of HBV DNA in immunized children born to HBsAg‐positive mothers, years after being diagnosed with occult HBV infection

Abstract

In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended.

Occult hepatitis B virus infection in immunized children born to carrier mothers

“…Therefore, it might have been necessary to maintain the anti‐HBs titers over certain levels. Sadeghi et al . reported that all 17 children diagnosed with OBI after immunoprophylaxis had ultimately cleared the virus before the age of 7 years.…”

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

“…In agreement with our findings, the study by Sadeghi et al discovered that HBV DNA disappeared in 94% (16/17) of the OBI-positive children 36 months after the initial sampling. HBV DNA was also undetectable in the still OBI-positive child eighteen months later [12]. They therefore claimed the clearance of HBV in those children.…”

“…In previous studies, 50.0% to 100.0% of the OBI-positive infants of HBsAg-positive mothers demonstrated negativity for anti-HBc [3–6,12]. It seems to deviate from the consensus that anti-HBc is the lifelong marker of past exposure to or present infection with HBV [17].…”

“…The incidence was likely to be even lower since 80.0% (4/5) of them were under 24 months of age. Indeed, at the second sampling 36 months later, anti-HBc disappeared in 80.0% (4/5) of them, leading to a final anti-HBc positivity rate of about 5.9% (1/17) [12]. We assume that strong immune pressure derived from passive-active immunization against HBV could allow the establishment of a low-dose HBV infection without sufficient antigens to stimulate and maintain the maturation of immune memory, which was supported by discoveries in woodchuck infection model that exposure to low levels of HBV DNA (<10 3 virions) might develop into anti-HBc seronegative infection [19].…”

“…Possible risk factors for OBI in immunized infants of HBsAg-positive mothers remain uncertain in previous studies [3–6,12]. Maternal HBeAg and HBV DNA at high levels in circulation might contribute to OBI status in their neonates after immunization [4,5].…”