Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Infections Post Transplant

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Bone Marrow Transplantation volume 33, pages 925–929 (2004)Cite this article

Summary:

Hepatitis B virus (HBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is well known in HBsAg-positive carriers but has only occasionally been reported in patients with resolved HBV infection. We investigated six allo-HSCT recipients with pretransplant anti-HBs and anti-HBc antibodies for serologic markers of HBV infection and for the presence of HBV-DNA in serum. Reverse seroconversion, that is, reappearance of HBsAg after a gradual loss of anti-HBs, but no severe liver damage was observed in three patients at 14, 22 and 12 months after HSCT, respectively. There was an increase in HBV-DNA concentration prior to reverse seroconversion. One patient was repeatedly HBV-DNA positive (102–103 copies/ml) without reverse seroconversion. Sequencing of the HBsAg and precore region derived from the four HBV-DNA-positive patients showed no relevant mutations. In conclusion, this study demonstrated a high risk (50%) of reverse seroconversion in allo-HSCT recipients with resolved HBV infection. A highly sensitive HBV-DNA assay (TaqMan-PCR) allowed early identification of the individual patients at risk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Lau GK, Liang R, Chiu EK et al. Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study. Bone Marrow Transplant 1997; 19: 795–799.

    Article  CAS  PubMed  Google Scholar 

  2. Strasser SI, McDonald GB . Hepatitis viruses and hematopoietic cell transplantation: a guide to patient and donor management. Blood 1999; 93: 1127–1136.

    CAS  PubMed  Google Scholar 

  3. Michalak TI, Pasquinelli C, Guilhot S, Chisari FV . Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest 1994; 93: 230–239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rehermann B, Ferrari C, Pasquinelli C, Chisari FV . The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 1996; 2: 1104–1108.

    Article  CAS  PubMed  Google Scholar 

  5. Weinberger KM, Wiedenmann E, Böhm S, Jilg W . Sensitive and accurate quantitation of hepatitis B virus DNA using a kinetic fluorescence detection system (TaqMan PCR). J Virol Methods 2000; 85: 75–82.

    Article  CAS  PubMed  Google Scholar 

  6. Knöll A, Rohrhofer A, Kochanowski B et al. Prevalence of precore mutants in anti-HBe-positive hepatitis B virus carriers in Germany. J Med Virol 1999; 59: 14–18.

    Article  PubMed  Google Scholar 

  7. Weinberger KM, Kreuzpaintner EA, Hottenträger B et al. Mutations in the S-gene of hepatitis B virus (HBV) isolates from chronic carriers with anti-HBc as the only serological marker of HBV infection. In: Rizetto M, Purcell RH, Gerin JL, Verme G (eds) Viral Hepatitis and Liver Disease. Edizioni Minerva Medica: Turin, 1997; pp 138–143.

    Google Scholar 

  8. Dhedin N, Douvin C, Kuentz M et al. Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc. Transplantation 1998; 66: 616–619.

    Article  CAS  PubMed  Google Scholar 

  9. Seth P, Alrajhi AA, Kagevi I et al. Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease. Bone Marrow Transplant 2002; 30: 189–194.

    Article  CAS  PubMed  Google Scholar 

  10. Chen PM, Fan S, Liu CJ et al. Changing of hepatitis B virus markers in patients with bone marrow transplantation. Transplantation 1990; 49: 708–713.

    Article  CAS  PubMed  Google Scholar 

  11. Chen PM, Fan S, Liu JH et al. Reactivation of hepatitis B virus in two chronic GVHD patients after transplant. Int J Hematol 1993; 58: 183–188.

    CAS  PubMed  Google Scholar 

  12. Martin BA, Rowe JM, Kouides PA, DiPersio JF . Hepatitis B reactivation following allogeneic bone marrow transplantation: case report and review of the literature. Bone Marrow Transplant 1995; 15: 145–148.

    CAS  PubMed  Google Scholar 

  13. Kostaridou S, Ladis V, Kattamis A et al. HBeAg-negative hepatitis B in a previously thalassemic patient during immunosuppressive therapy for chronic GVHD. Bone Marrow Transplant 1998; 22: 919–921.

    Article  CAS  PubMed  Google Scholar 

  14. Li Volti S, Pizzarelli G, Galimberti M et al. Clinical and biochemical reactivation of HBV infection in a thalassemic patient after bone marrow transplantation. Infection 1998; 26: 58–60.

    Article  CAS  PubMed  Google Scholar 

  15. Picardi M, Selleri C, De Rosa G et al. Lamivudine treatment for chronic replicative hepatitis B virus infection after allogeneic bone marrow transplantation. Bone Marrow Transplant 1998; 21: 1267–1269.

    Article  CAS  PubMed  Google Scholar 

  16. Iwai K, Tashima M, Itoh M et al. Fulminant hepatitis B following bone marrow transplantation in an HBsAg-negative, HBsAb-positive recipient; reactivation of dormant virus during the immunosuppressive period. Bone Marrow Transplant 2000; 25: 105–108.

    Article  CAS  PubMed  Google Scholar 

  17. Nordbo SA, Skaug K, Holter E et al. Reactivation of hepatitis B virus infection in an anti-HBc and anti-HBs positive patient after allogeneic bone marrow transplantation. Eur J Haematol 2000; 65: 86–87.

    Article  CAS  PubMed  Google Scholar 

  18. Sakamaki H, Sato Y, Mori SI et al. Hepatitis B virus reactivation in a patient with chronic GVHD after allogeneic peripheral blood stem cell transplantation. Int J Hematol 2001; 74: 342–346.

    Article  CAS  PubMed  Google Scholar 

  19. Goyama S, Kanda Y, Nannya Y et al. Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation. Leuk Lymphoma 2002; 43: 2159–2163.

    Article  CAS  PubMed  Google Scholar 

  20. Hashino S, Nozawa A, Izumiyama K et al. Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation. Bone Marrow Transplant 2002; 29: 361–363.

    Article  CAS  PubMed  Google Scholar 

  21. Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA . Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci U S A 1986; 83: 1627–1631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen PM, Yao NS, Wu CM et al. Detection of reactivation and genetic mutations of the hepatitis B virus in patients with chronic hepatitis B infections receiving hematopoietic stem cell transplantation. Transplantation 2002; 74: 182–188.

    Article  PubMed  Google Scholar 

  23. Miura Y, Takamatsu H, Okumura H et al. Allogeneic bone marrow transplantation for a patient complicated by chronic hepatitis due to precore mutant hepatitis B virus: failure of management with interferon-alpha therapy. Am J Hematol 1997; 54: 344–345.

    Article  CAS  PubMed  Google Scholar 

  24. McIvor C, Morton J, Bryant A et al. Fatal reactivation of precore mutant hepatitis B virus associated with fibrosing cholestatic hepatitis after bone marrow transplantation. Ann Intern Med 1994; 121: 274–275.

    Article  CAS  PubMed  Google Scholar 

  25. Dienstag JL, Perrillo RP, Schiff ER et al. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med 1995; 333: 1657–1661.

    Article  CAS  PubMed  Google Scholar 

  26. Henkes M, Martin S, Einsele H, Aulitzky WE . Successful antiviral treatment for fulminant reactivated hepatitis B after autologous stem cell transplantation and prophylaxis during subsequent allogeneic stem cell transplantation. Ann Hematol 2002; 81: 343–346.

    Article  CAS  PubMed  Google Scholar 

  27. Honkoop P, Niesters HG, de Man RA et al. Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. J Hepatol 1997; 26: 1393–1395.

    Article  CAS  PubMed  Google Scholar 

  28. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. Cytotherapy 2001; 3: 41–54.

  29. Szmuness W, Harley E, Ikran H . Sociodemographic aspects of the epidemiology of hepatitis B. In: Vyas GN, Cohen SN, Schmid R (eds). Viral Hepatitis. Franklin Institute press: Philadelphia, 1978; p 297.

    Google Scholar 

  30. Jilg W, Hottenträger B, Weinberger K et al. Prevalence of markers of hepatitis B in the adult German population. J Med Virol 2001; 63: 96–102.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany

    A Knöll, S Boehm & W Jilg

  2. Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

    J Hahn & E Holler

Authors
  1. A Knöll
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Boehm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Holler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W Jilg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Knöll.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knöll, A., Boehm, S., Hahn, J. et al. Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 33, 925–929 (2004). https://doi.org/10.1038/sj.bmt.1704457

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704457

Keywords

This article is cited by

Search

Advanced search

Quick links