title: Hepatitis B immunoprophylaxis failure and the presence of hepatitis B surface gene mutants in the affected children.
abstract: Hepatitis B virus (HBV) infection is usually vertically transmitted from the mother to child during birth in Asian countries. Despite immunization, immunoprophylaxis failure is well-documented. The aim of the study was to study immunoprophylaxis failure rate in the cohort of infants delivered by chronic HBV-infected mothers and to determine risk factors for failure. This was an observational study involving chronic hepatitis B infected mothers seen at a tertiary care center in Singapore between June 2009 and December 2013. Infants born to these mothers were recruited after they had completed the recommended vaccination schedule. Serological testing for the children was performed 3 months after completion of the last dose of vaccine. HBV surface gene sequencing was carried out if HBV DNA was detectable in the children. Among the 161 mothers enrolled, most were HBeAg negative. HBeAg positive mothers were younger and had a significantly higher viral load (6.5 log) as compared to HBeAg negative mothers (1.35 log) (P < 0.001). Four children (2.6%) were found to have immunoprophylaxis failure. Two occurred in children delivered by mothers with extremely high viral load of more than 5 × 10(7)  IU/ml. HBV surface gene mutations were detected in most children (3 out of 4) with immunoprophylaxis failure. The overall effectiveness of the hepatitis B vaccination program was high. High maternal viral load and presence of surface gene mutants may be potential contributors.
authors.affiliation: Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.|Department of Paediatrics, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
authors.forename: Le Ye
authors.initials: le Y
authors.lastname: Lee
authors.affiliation: Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.|Department of Paediatrics, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
authors.forename: Marion
authors.initials: M
authors.lastname: Aw
authors.affiliation: Department of Obstetrics & Gynecology, National University Hospital, Singapore.
authors.forename: Mary
authors.initials: M
authors.lastname: Rauff
authors.affiliation: Division of Gastroenterology & Hepatology, Medicine Cluster, National University Hospital, Singapore.
authors.forename: Kah-Sin
authors.initials: KS
authors.lastname: Loh
authors.affiliation: Division of Gastroenterology & Hepatology, Medicine Cluster, National University Hospital, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Division of Gastroenterology & Hepatology, Medicine Cluster, National University Hospital, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore.
authors.forename: Guan Huei
authors.initials: GH
authors.lastname: Lee
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007114:Immunization / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D050505:Mutant Proteins / Q000235:genetics*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012846:Singapore; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D050505:Mutant Proteins
keywords: hepatitis B chronic carrier mothers; hepatitis B surface gene mutations; immunoprophylaxis failure in children; maternal HBV DNA (viral load); vertical transmission