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Neonatal hepatitis B vaccination protects mature adults from occult virus infection

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Abstract

Background

Among elder children/young adults who received hepatitis B virus (HBV) vaccination during infancy, the serological status of HBsAg-negative and anti-HBc-positive [HBsAg(–)/anti-HBc(+)] was frequently reported, indicating potential occult HBV infection (OBI). It is required to define the long-term protection of neonatal vaccination against OBI in their mature adulthood.

Methods

Building upon the 1983–1990 established Qidong Hepatitis B Intervention Study, we sampled 10% of the 28–35-year-old participants, who remained in the cohort by 2012. Each participant was tested for serological markers of HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc. HBV-DNA and relaxed circular DNA (rcDNA) were determined in some HBsAg(–)/anti-HBc(+) individuals.

Results

Totally, 3615 individuals from the neonatal vaccination group and 3100 individuals from the control group donated blood samples, respectively. In the vaccination group, the prevalence of HBsAg was 1.58% (57/3615), HBsAg(–)/anti-HBc(+) was 4.70% (170/3615), significantly lower than in the control group, which was 7.45% (231/3100) and 19.48% (640/3100) respectively (all p < 0.001). With aging, HBsAg(–)/anti-HBc(+) prevalence increased in the sampled participants from the control group (pfor trend < 0.001), but uncertain from the vaccination group. Of HBsAg(–)/anti-HBc(+), HBV-DNA was detected in 13.08% (17/130) from the vaccination group, and in 4.18% (12/287) from the control group. HBV rcDNA was detected in most sera that were tested positive for HBV-DNA.

Conclusions

OBI occurred in some vaccinated adults. However, neonatal HBV vaccination kept the effective protection against OBI in mature adults.

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Data availability

The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data are available for researchers who meet the criteria for access to confidential data from the Ethics Committee, National Cancer Center /Cancer Hospital, Chinese Academy of Medical Sciences. The administrator at the Office of Science and Research, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences can be contacted to data request by email: keyanchu@cicams.ac.cn and quchf@cicams.ac.cn.

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Acknowledgements

We sincerely thank all participants and their families in the Qidong Hepatitis B Intervention Study (QHBIS), and all staff who contributed to the initial intervention, and follow-up studies.

Funding

This work was supported by Key Research Projects for Precision Medicine (2017YFC0908103), Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences (CIFMS, 2019-I2M-2-004, Cohort study of the esophageal cancer and liver cancer; and 2016-I2M-1-007), State Key Projects Specialized on Infectious Diseases (2017ZX10201201-006), and National Natural Science Foundation Fund (81972628, 81571620).

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Author notes

  1. Ruijun Wang, Chang Liu, and Taoyang Chen have equally contributed to this work.

Authors and Affiliations

  1. State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan South Lane, Beijing, 100021, People’s Republic of China

    Ruijun Wang, Chang Liu, Yuting Wang & Chunfeng Qu

  2. Jiangsu, Qidong Liver Cancer Institute & Qidong People’s Hospital, Qidong, 226200, People’s Republic of China

    Taoyang Chen, Chunsun Fan & Lingling Lu

  3. State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China

    Fengmin Lu

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  1. Ruijun Wang
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Contributions

CQ designed and supervised the study, drafted and finalized the manuscript. RW, CL, TC, YW, CF, LL and FL performed the data collection and analysis. RW, CL and TC drafted the manuscript. FL provided the key reagents for HBV rcDNA detection and revised the manuscript.

Corresponding author

Correspondence to Chunfeng Qu.

Ethics declarations

Conflict of interest

Ruijun Wang, Chang Liu, Taoyang Chen, Yuting Wang, Chunsun Fan, Lingling Lu, Fengmin Lu, and Chunfeng Qu declare that they have no conflict of interest.

Ethics approval

The study protocol (NCC201709011) was approved by the Ethical Committees of the National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences (NCC/CH-CAMS). All procedures performed in studies involving human participants were in accordance with the ethical standards of 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate

All participants provided written informed consent before any study procedures were provided.

Consent for publication

All authors of this manuscript have read and approved the final submitted version, and are aware that they are listed as an author on this paper.

Animal research

This article does not contain any studies with animals performed by any of the authors.

Clinical trials registration

The current study was based on a cross-sectional investigation of Qidong Hepatitis B Intervention Study (QHBIS). Original QHBIS was registered with Clinical Trials.gov number NCT00222664.

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Cite this article

Wang, R., Liu, C., Chen, T. et al. Neonatal hepatitis B vaccination protects mature adults from occult virus infection. Hepatol Int 15, 328–337 (2021). https://doi.org/10.1007/s12072-021-10156-z

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