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Infectivity of blood products from donors with occult hepatitis B virus infection

Authors

  • Jean-Pierre Allain,

    Scientific Affairs Consultant, Corresponding author
    1. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    2. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    3. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    4. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    5. Regional Blood Center, Oviedo, Spain
    6. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    7. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    8. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    9. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    10. National Health Service Blood and Transplant England, Cambridge, UK
    11. Paris, France
    12. Paul Ehrlich Institute, Langen, Germany
    • Department of Haematology, University of Cambridge, Cambridge, UK
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  • Ivanka Mihaljevic,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Maria Isabel Gonzalez-Fraile,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Knut Gubbe,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Lene Holm-Harritshøj,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Jose Maria Garcia,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Ewa Brojer,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Christian Erikstrup,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Mona Saniewski,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Lorenz Wernish,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Lydia Bianco,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Henrik Ullum,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Daniel Candotti,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Nico Lelie,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Wolfram H. Gerlich,

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • Michael Chudy

    1. Department of Haematology, University of Cambridge, Cambridge, UK
    2. Croatian Institute of Transfusion Medicine, Zagreb, Croatia
    3. Centro de Hemoterapia de Castilla y León, Valladolid, Spain
    4. German Red Cross, Institute of Transfusion Medicine, Plauen, Germany
    5. Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark
    6. Regional Blood Center, Oviedo, Spain
    7. Institute of Hematology and Transfusion Medicine, Warsaw, Poland
    8. Department of Clinical Immunology, Arhus University Hospital, Arhus, Denmark
    9. Institute of Medical Virology, Justus Liebig University, Giessen, Germany
    10. MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    11. National Health Service Blood and Transplant England, Cambridge, UK
    12. Paris, France
    13. Paul Ehrlich Institute, Langen, Germany
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  • This study was supported in part by grants from the National Health Service Blood and Transplant, the International Society of Blood Transfusion Foundation, and Novartis Vaccines and Diagnostics to JPA and by the Robert Koch Institute to WHG.

Address reprint requests to: Jean-Pierre Allain, Department of Haematology, Cambridge Blood Centre, Long Road, Cambridge CB2 2PT, UK; e-mail: jpa1000@cam.ac.uk.

Abstract

Background

Occult hepatitis B virus (HBV) infection (OBI) is identified in 1:1000 to 1:50,000 European blood donations. This study intended to determine the infectivity of blood products from OBI donors.

Study Design and Methods

Recipients of previous donations from OBI donors were investigated through lookback (systematic retrieval of recipients) or traceback (triggered by clinical cases). Serologic and genomic studies were undertaken on consenting donors and recipients. Multiple variables potentially affecting infectivity were examined.

Results

A total of 45 of 105 (42.9%) donor-recipients pairs carried antibodies to HBV core (anti-HBc) as evidence of previous HBV infection. Subtracting 15% of anti-HBc population background, the adjusted transmission rate was 28%. Anti-HBc prevalence increased to 28 of 44 (63.8%) in unvaccinated recipients receiving anti-HBs–negative OBI blood products. In contrast, four of 26 (15.4%) recipients of anti-HBs–positive products were anti-HBc positive. Transmission with anti-HBs–negative products depended on volume of plasma transfused (85%-100% with 200 mL of fresh frozen plasma [FFP], 51% with 50 mL in platelet concentrates [PCs], and 24% with 20 mL in red blood cells [RBCs], p < 0.0001 FFP vs. RBCs). The 50% minimum infectious dose of OBI HBV DNA was estimated at 1049 (117-3441) copies. Donor and recipient strains sequence homology of at least 99% confirmed transfusion-transmitted infection in 10 cases and excluded it in one case.

Conclusion

Blood products from donors with OBI carry a high risk of HBV transmission by transfusion. This risk is dependent on presence of anti-HBs and viral dose. This may justify safety measures such as anti-HBc and HBV nucleic acid test screening depending on epidemiology.

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