Limited benefit of hepatitis B immunoglobulin prophylaxis in children of hepatitis B e antigen-negative mothers

<p><b>INTRODUCTION</b>In 2006, Singapore adopted the universal hepatitis B immunoglobulin (HBIg) policy. Since then, all infants of hepatitis B surface antigen (HBsAg)-positive mothers receive HBIg, irrespective of maternal hepatitis B e antigen (HBeAg) status. However, the benefits of HBIg for infants of HBeAg-negative mothers are unclear. We compared the vertical transmission rates among children of HBeAg-negative mothers who were given HBIg versus a retrospective cohort who were not given HBIg, to determine its protective effect.</p><p><b>METHODS</b>This observational study involved pregnant HBsAg-positive women seen at National University Hospital, Singapore, between June 2009 and December 2013. If the infants of these mothers completed the recommended vaccination schedule, they were recruited into the study, along with their older siblings. Serological testing for the children was performed three months after completion of the last dose of vaccine, and hepatitis B virus (HBV) surface gene sequencing was carried out if HBV DNA was detected.</p><p><b>RESULTS</b>A total of 111 infants and 47 siblings were recruited. 2 (1.5%) children were found to have vertical transmission despite receiving HBIg, while no incidences of vertical transmission were found among the historical controls who did not receive HBIg (p = 1.00).</p><p><b>CONCLUSION</b>The overall effectiveness of the hepatitis B vaccination programme for children of HBsAg-positive mothers was high, regardless of HBIg administration. The addition of HBIg did not appear to confer additional benefits, in terms of vertical transmission rate, among infants born to HBeAg-negative mothers.</p>

Prevalence of genotype D in chronic liver disease patients with occult HBV infection in northern region of India.

Background: Etiology of nearly 30% cases of chronic viral hepatitis remains undetected. Occult HBV infection (OBI) has emerged as an important clinical entity in this scenario. Apart from prevalence and clinical outcome of OBI patients genotype was determined in northern region of India. Materials and Methods: A total of 847 patients with chronic liver disease (CLD) were screened for common viral etiologies and others serological markers of HBV. Amplifi cation of surface, precore and polymerase genes of HBV was performed in patients negative for other etiologies. Genotyping and sequencing of the precore region was performed for OBI cases. Results: Twenty-nine (7.61%) cases of OBI were identifi edof which 9 had chronic liver disease (CHD), 11 liver cirrhosis (LC) and 9 hepatocellular carcinoma (HCC). Majority of OBI cases were detected by amplifi cation of surface gene 26 (89.6%), followed by pre-core gene 12 (41.3%). Their liver functions tests were signifi cantly deranged in comparison to overt HBV cases. IgG anti HBc was present in 8 (27.6%) OBI cases. Mutation was observed in 8 (32%) in pre-core region at nt. 1896 of overt HBV cases. Genotype D was the predominant genotype. In conclusion: OBI in our study was characterized by predominance of genotype D and more severe clinical and biochemical profi le in comparison to overt HBV. IgG anti HBc positivity could be utilized as a marker of OBI. We recommend use of sensitive nested PCR for diagnosis of OBI, amplifying at least surface and precore gene.

Surface gene variants of hepatitis B virus of the co-existence of HBsAg and HBsAb in patients with chronic HBV infection / 中华微生物学和免疫学杂志

ObjectiveTo analyze the characteristics of S gene varivants of patients with chronic hepatitis B virus infection with coexistence of HBsAg and HBsAb.MethodsHBV DNA S gene regions were amplified and sequenced in 26 HBsAg-positive/HBsAb-positive patients (test group) and the newly diagnosed 39 HBsAg-positive/HBsAb-negative patients (control group).The sequencing results and amino acid variants of this region were analyzed.ResultsThe amino acid variants were significantly more frequent in test group than in control group among the complete S gene region (P＜0.05).In addition,a significantly bigher amino acid variants arose in patients group versus control group in HBsAg major hydrophilic region (MHR),especially the first loop area of a-determinant (6.69％ vs 0.89％,P＜0.05).ConclusionThe coexistence of HBsAg and HBsAb in patients with chronic HBV infected might be related to the emergence of S gene variants in and around HBsAg a-determinant especially in the first loop area.

The Incidence Rate of Hepatitis B Virus Surface Gene Variants in Korean Children with Immunoprophylaxis Failure of Perinatal Infection / 대한간학회지

BACKGROUND/AIMS: Perinatal infection with hepatitis B virus (HBV) may occur despite immunoprophylaxis. One of the important mechanisms for perinatal prophylaxis failure, might include HBV surface gene variants. Therefore, we screened Korean children, in whom perinatal prophylaxis failed, for HBV surface gene variants. METHODS: Thirty-one children with perinatal HBV prophylaxis failure were selected. To amplify the major hydrophilic region of the HBV surface gene, nested PCR with primers targeted to nucleotides 237 to 706 was performed, and then sequencing was done. RESULTS: All cases were shown to be PCR positive for HBV-DNA and genotype C. Nine out of 31 (29%) with perinatal prophylaxis failure had a nucleotide substitution at the major hydrophilic region of the gene; but only two cases (6.5%) had an amino acid substitution. One case was infected by wild type and variants of I126S, and the other by wild type and S114A+I126S, respectively. CONCLUSIONS: In Korea, compared to the previous studies of other nations, gene surface variants such as G145R do not appear to play an important role in perinatal immunoprophylaxis failure.

Perinatal Hepatitis B Virus Infection: Viral Factors in the Mechanism of Perinatal Immunoprophylaxis Failure / 소아과

Perinatal hepatitis B virus(HBV) infection may occur despite combined immunoprophylaxis with hepatitis B immunoglobulin and vaccines. Although the mechanism of perinatal prophylaxis still has been obscure, it could be due to:in utero infection; host factors as the personal immunological differences of HLA or cytokine gene; viral factors as a high maternal HBV-DNA level or the presence of surface gene variants; or other factors as the differences of composition, quality, dosage, frequencies, timing and injection site of HBV vaccine or immunoglobulin. To investigate the clinical significance of variant in HBV surface gene in Korea, DNA sequence analysis of the major hydrophilic region was performed and reviewed the related articles. The variant rate observed in perinatal HBV immunoprophylaxis failure children in comparison to other studies was 6.45% versus 14-40%. And perinatal infection could be prevented by immunoprophylaxis in children, even though mothers had infection with variants in HBV surface gene. These findings suggest that the variants on the surface gene are not playing an important role in perinatal immunoprophylaxis failure in Korea. Also, a fact that the higher maternal DNA level was strongly associated with immunoprophylaxis failure was demonstrated. Therefore, the conditions, like maternal viral composition, the degree of maternal DNA level, the status of host immune system should be associated with the outcome of immunoprophylaxis in perinatal infection simultaneously.