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  • Quasispecies characteristic in “a” determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case–control study

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Hepatology
Original research
Quasispecies characteristic in “a” determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case–control study
  1. Yiwei Xiao1,
  2. Kuixia Sun1,2,
  3. Zhongping Duan3,
  4. Zhixiu Liu1,
  5. Yi Li1,
  6. Ling Yan1,
  7. Yarong Song1,
  8. Huaibin Zou3,
  9. Hui Zhuang1,
  10. Jie Wang1,
  11. Jie Li1
  1. 1 Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
  2. 2 Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, P.R. China
  3. 3 Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100054, P.R. China
  1. Correspondence to Associate Professor Jie Li, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China; jieli{at}bjmu.edu.cn; Associate Professor Jie Wang, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China; wangjie2015{at}bjmu.edu.cn; Professor Hui Zhuang, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China; zhuangbmu{at}126.com

Abstract

Objective This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants.

Design In this prospective nested case–control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of “a” determinant region, and were compared between the two groups.

Results The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of “a” determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of “a” determinant region, and the corresponding predictive values were tentatively set up.

Conclusions HBV quasispecies with a more complex mutant spectrum in “a” determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.

  • hepatitis B virus
  • mother-to-child transmission
  • quasispecies
  • “a” determinant region
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/gutjnl-2019-318278

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    Footnotes

    • YX and KS contributed equally.

    • Correction notice This article has been corrected since it published Online First. The correspondence details have been corrected for Professor Hui Zhuang.

    • Contributors YX and KS are joint first authors. JL obtained funding. JL and JW designed the study. YX, KS, ZL, YL, LY and YS performed the study. YX, KS, JL, JW, HZ, ZD and HZ analysed data. YX drafted the manuscript. JL, JW and HZ contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript. JL, JW and HZ are the study guarantors.

    • Funding This study was supported by grants from the National Major Scientific and Technological Special Project during the Thirteenth Five-year Plan Period (2017ZX10201201003); The National Natural Science Foundation of China (81571949).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethical approval The experimental protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. This study was approved by the Ethics Committee of Peking University Health Science Center. Written informed consent was obtained from each subject.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.