Skip to main content

Advertisement

Log in

Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Collaborators GBDHB. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet Gastroenterol Hepatol. 2022;7:796–829.

    Article  Google Scholar 

  2. Seto WK, Lo YR, Pawlotsky JM, et al. Chronic hepatitis B virus infection. Lancet. 2018;392:2313–24.

    Article  PubMed  Google Scholar 

  3. Smalls DJ, Kiger RE, Norris LB, et al. Hepatitis B Virus reactivation: risk factors and current management strategies. Pharmacotherapy. 2019;39:1190–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156-65.

    Article  CAS  PubMed  Google Scholar 

  5. Myint A, Tong MJ, Beaven SW. Reactivation of hepatitis B virus: a review of clinical guidelines. Clin Liver Dis Hoboken. 2020;15:162–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Knoll A, Boehm S, Hahn J, et al. Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transpl. 2004;33:925–9.

    Article  CAS  Google Scholar 

  7. Marusawa H, Imoto S, Ueda Y, et al. Reactivation of latently infected hepatitis B virus in a leukemia patient with antibodies to hepatitis B core antigen. J Gastroenterol. 2001;36:633–6.

    Article  CAS  PubMed  Google Scholar 

  8. Tong MJ, Sampliner RE, Govindarajan S, et al. Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis. Hepatology. 1987;7:713–8.

    Article  CAS  PubMed  Google Scholar 

  9. Obara N, Inoue J, Endo H, et al. Spontaneous reactivation of hepatitis B virus with S gene mutations in an elderly patient with diabetic nephropathy. Clin J Gastroenterol. 2020;13:914–9.

    Article  PubMed  Google Scholar 

  10. Takakusagi S, Takagi H, Yokoyama Y, et al. Spontaneous reactivation of hepatitis B virus with a frameshift mutation in the precore region in an elderly hepatitis B virus carrier with lifestyle-related diseases. Clin J Gastroenterol. 2021;14:1202–10.

    Article  PubMed  Google Scholar 

  11. Kamitsukasa H, Iri M, Tanaka A, et al. Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection. J Med Virol. 2015;87:589–600.

    Article  CAS  PubMed  Google Scholar 

  12. Kim DH, Kim SB. Hepatic failure by spontaneous reactivation of hepatitis B Virus without a trigger factor in a patient with anti-HBs. Case Rep Gastroenterol. 2018;12:286–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mulyanto Depamede SN, Surayah K, et al. Identification and characterization of novel hepatitis B virus subgenotype C10 in Nusa Tenggara. Indonesia Arch Virol. 2010;155:705–15.

    Article  PubMed  Google Scholar 

  14. Usuda S, Tsuda F, Gotanda T, et al. A solid-phase enzyme immunoassay for the common and subtypic determinants of hepatitis B surface antigen with monoclonal antibodies. J Immunol Methods. 1986;87:203–10.

    Article  CAS  PubMed  Google Scholar 

  15. Ohnuma H, Takai E, Machida A, et al. Synthetic oligopeptides bearing a common or subtypic determinant of hepatitis B surface antigen. J Immunol. 1990;145:2265–71.

    Article  CAS  PubMed  Google Scholar 

  16. Okamoto H, Omi S, Wang Y, et al. The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. Mol Immunol. 1989;26:197–205.

    Article  CAS  PubMed  Google Scholar 

  17. Beran A, Mhanna M, Haghbin H, et al. A case of hepatitis B virus reactivation triggered by acute Epstein-Barr virus infection. Cureus. 2021;3: e18676.

    Google Scholar 

  18. Pei R, Grund S, Verheyen J, et al. Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected patient with isolated anti-hepatitis B core antibodies. Virol J. 2014;11:9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sagnelli C, Montella L, Grimaldi P, et al. COVID-19 as another trigger for HBV Reactivation: clinical case and review of literature. Pathogens. 2022;11:816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Michalak TI, Pasquinelli C, Guilhot S, et al. Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest. 1994;93:230–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shi Y, Zheng M. Hepatitis B virus persistence and reactivation. BMJ. 2020;370:m2200.

    Article  PubMed  Google Scholar 

  22. Sakamoto K, Umemura T, Ito K, et al. Virological factors associated with the occurrence of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection analyzed through ultradeep sequencing. J Infect Dis. 2020;221:400–7.

    CAS  PubMed  Google Scholar 

  23. Kramvis A, Arakawa K, Yu MC, et al. Relationship of serological subtype, basic core promoter and precore mutations to genotypes/subgenotypes of hepatitis B virus. J Med Virol. 2008;80:27–46.

    Article  CAS  PubMed  Google Scholar 

  24. Lazarevic I, Banko A, Miljanovic D, et al. Immune-escape hepatitis B virus mutations associated with viral reactivation upon immunosuppression. Viruses. 2019;11:778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lada O, Benhamou Y, Poynard T, et al. Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of “a” determinant variants. J Virol. 2006;80:2968–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Purdy MA. Hepatitis B virus S gene escape mutants. Asian J Transfus Sci. 2007;1:62–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lazarevic I. Clinical implications of hepatitis B virus mutations: recent advances. World J Gastroenterol. 2014;20:7653–64.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wang J, Zhu B, Lu M, et al. Hepatitis B virus preS/S gene mutations and their clinical implications. Annals Blood. 2017;2:17.

    Article  Google Scholar 

  29. Wu C, Zhang X, Tian Y, et al. Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication. J Gen Virol. 2010;91:483–92.

    Article  CAS  PubMed  Google Scholar 

  30. Inoue J, Nakamura T, Masamune A. Roles of hepatitis B virus mutations in the viral reactivation after immunosuppression therapies. Viruses. 2019;11:457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Oon C, Lim G, Ye Z, et al. Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine. 1995;13:699–702.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: Tokio Sasaki, Akio Miyasaka. Investigation: Masaharu Takahashi, Hiroaki Okamoto. Writing-original draft: Tokio Sasaki. Writing, review, and editing: Keisuke Kakisaka, Akio Miyasaka, Masao Nishiya, Naoki Yanagawa, Hidekatsu Kuroda, Takayuki Matsumoto, Masaharu Takahashi, and Hiroaki Okamoto. Approval of final manuscript: All authors.

Corresponding author

Correspondence to Tokio Sasaki.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Human rights

All the procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from the patient to publish the clinical and virological findings.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 86 kb)

Supplementary file2 (PDF 91 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sasaki, T., Kakisaka, K., Miyasaka, A. et al. Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection. Clin J Gastroenterol (2024). https://doi.org/10.1007/s12328-024-01984-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12328-024-01984-1

Keywords

Navigation