High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG

Abstract

Occult hepatitis B virus (HBV) infection is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable hepatitis B surface antigen (HBsAg). The frequency of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA assays. We aimed at determining the prevalence of occult HBV infection in a high risk group of children who developed HBV infection despite immunoprophylaxis. The sera of 75 children born to HBsAg-positive mothers previously immunized by HBIG and prophylaxic vaccine regimen were assayed for HBV DNA by real-time PCR. Subsequently, the samples were tested using a sensitive standard PCR, with an independent set of primers for all HBV genes, and analyzed by direct sequencing. HBV DNA was detected in 21/75 (28%) children, and ranged between 77 and 9240 copies/ml. All were positive for anti-HBs. Five (24%) children were found to be positive for anti-HBc, while anti-HBc-only positive individuals were not observed. Eight isolates (38%) did not carry any mutation. Thirteen infected children (62%) had at least one mutation in regions known to be involved in functional and/or immune epitope activity. Ten had G145R mutations. HBV occult infection seems to be relatively frequent in immunized children born to HBsAg-positive mothers. HBsAg negativity is not sufficient to completely exclude HBV DNA presence. These findings emphasize the importance of considering occult HBV infection in hypo-endemic areas.