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Hepatitis B virus infection in children of HBV-related chronic liver disease patients: a study of intra-familial HBV transmission

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Abstract

Background

HBV-infected patients are potential sources of intra-familial transmission. We studied HBV transmission and molecular characteristics within families of HBV-related chronic liver disease (CLD) patients.

Methods

Family members [index cases (ICs), spouses, and 1–18-year-old children] of HBV-related CLD patients were tested for HBsAg, anti-HBc, and anti-HBs. HBsAg-positive subjects were tested for HBeAg/anti-HBe. Anti-HBc-positive children together with their family members were further investigated for HBV DNA. Sequences of positive isolates were analyzed over surface, precore (PC) and basal core promoter (BCP) regions.

Results

Among 94 children of 46 ICs, the prevalence of HBsAg, anti-HBc, and anti-HBs was 10 (10.6 %), 19 (20.2 %), and 46 (48.9 %), respectively. Thirty-eight (40.4 %) children were seronegative, indicating susceptibility to HBV infection. HBV DNA was identified in all ICs, 4 spouses, and 16 children. Having both parents with HBsAg positive and at least two HBV carriers in the households were significant risk factors of intra-familial transmission. HBV genotype/subtype distributions were comparable between children and ICs/spouses, with predominance of genotype B. The majority of HBV DNA sequences found in children were identical to their corresponding ICs—particularly mothers—including mutation patterns in the surface, PC, and BCP regions. Recognized mutations associated with HBsAg detection and/or vaccination failure, T140I, T143S/M, G145R, and Y161F, were identified in 20 subjects; while mutations linked to HBeAg-defective variants, PC G1896A and BCP A1762T/G1764A, were found in 7 and 11 subjects, respectively.

Conclusions

Children of HBV-related CLD patients were at increased risk of HBV infection through multi-modal transmission routes despite negative parental HBsAg and HBeAg status.

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Acknowledgements

The authors would like to thank all children and parents who participated in this study. Special thanks are extended to the Division of Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia, for recruitment of patients. Sincere gratitude is expressed to the Eijkman Institute, Jakarta, for the molecular work support and to the academic staff of the Department of Pediatrics, Faculty of Medicine, University of Indonesia, for discussions and suggestions.

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    Authors and Affiliations

    1. Department of Child Health, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia

      Hartono Gunardi, Melanie Y. Iskandar & Pramita G. Dwipoerwantoro

    2. Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia

      Turyadi, Susan I. Ie & David H. Muljono

    3. Department of Internal Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia

      Rino A. Gani

    4. Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

      David H. Muljono

    5. Sydney Medical School, University of Sydney, Sydney, NSW, Australia

      David H. Muljono

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    1. Hartono Gunardi
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    Correspondence to David H. Muljono.

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    Funding

    This study was partly supported by a research grant from the Ministry for Research and Higher Education, Republic of Indonesia.

    Conflict of interest

    All authors declare that he/she has no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by The Committee of Medical Research Ethics of the Faculty of Medicine, University of Indonesia (no. 297/PT02.FK/ETIK/2009).

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    H. Gunardi and M. Y. Iskandar contributed equally.

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    Gunardi, H., Iskandar, M.Y., Turyadi et al. Hepatitis B virus infection in children of HBV-related chronic liver disease patients: a study of intra-familial HBV transmission. Hepatol Int 11, 96–104 (2017). https://doi.org/10.1007/s12072-016-9764-z

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