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Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

ABSTRACT: It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

SUBMITTER: Yao QQ

PROVIDER: S-EPMC3571284 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

Yao Qing-Qing QQ Dong Xiao-Lian XL Wang Xue-Cai XC Ge Sheng-Xiang SX Hu An-Qun AQ Liu Hai-Yan HY Wang Yueping Alex YA Yuan Quan Q Zheng Ying-Jie YJ

Clinical and vaccine immunology : CVI 20121219 2

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant wo ...[more]

PMID: 23254298

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Project description:BackgroundSelection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg), the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure.ResultsThree HBV variants (T123A, M133L and T143M) and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others.ConclusionsSingle amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of antigenicity changes found in Indonesian blood donors. This highlights the importance of evaluating the effects of protein structure alterations on the sensitivity of screening methods being used in detection of ongoing HBV infection, as well as the use of vaccines and immunoglobulin therapy in contributing to the selection of HBV variants.

Project description:HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t)ide analogue (NA) therapy (n = 4 [31%]; median clearance time,150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care.IMPORTANCE Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.

Project description:BackgroundHepatitis B infection seriously threatens global public health, especially in developing nations. Despite several investigations on HBV incidence, the national pooled prevalence remains unknown, particularly in populations at-risk at whom interventions should be primarily aimed.MethodsA comprehensive literature search of the following databases: Medline [PubMed], Scopus, Google Scholar, and Web of Science was conducted following the PRISMA guidelines. I-squared and Cochran's Q were used to measure the heterogeneity between the studies. Publications that matched the following were included: Primary studies published in Egypt from 2000 to 2022 reported HBV prevalence based on HBsAg. We excluded any studies that were not performed on Egyptians or that were performed on patients suspected of acute viral hepatitis or studies focusing on occult hepatitis or vaccination evaluation studies, or national surveys.ResultsThe systematic review included 68 eligible studies reporting a total of 82 incidences of HBV infection based on hepatitis B surface antigen with a total sample size of 862,037. The pooled national prevalence among studies was estimated to be 3.67% [95% CI; 3: 4.39]. Children under 20 with a history of HBV vaccination during infancy had the lowest prevalence of 0.69%. The pooled prevalence of HBV infection among pregnant women, blood donors, and healthcare workers was 2.95%, 1.8%, and 1.1%, respectively. While patients with hemolytic anemia and hemodialysis patients, patients with malignancies, HCC patients, and chronic liver disease patients had the highest prevalences at 6.34%, 25.5%, 18.6%, and 34%, respectively. Studies reporting HBV prevalence in urban settings compared to rural settings revealed a similar HBV prevalence of 2.43% and 2.15%, respectively. Studies comparing HBV prevalence in males and females revealed a higher prevalence among males (3.75%) than females (2.2%).ConclusionIn Egypt, hepatitis B infection is a significant public health issue. The blocking of mother-to-infant hepatitis B transmission, the scaling up of the scope of the existing vaccination program, and implementing new strategies, including screen-and-treat, may reduce the prevalence of the disease.

Dataset Information

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

Publications

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

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