Evaluation of occult hepatitis B infection in tissue donors: a multicenter analysis in Spain
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Traditionally, when antibody to the Hepatitis B core antigen (anti-HBc) and antibody to the Hepatitis B surface antigen (anti-HBs) are positive, the donor is considered suitable. However, the literature contains cases with this profile and circulating hepatitis B virus DNA. The aim of the study is to analyze the incidence of occult hepatitis B virus infection (OBI). Retrospective data were evaluated for deceased tissue donors in ten Tissue Establishments (Spain) during 2017. The data included demographic data and the serological markers for hepatitis B that each tissue establishment performed. A total number of 1933 tissue donors were evaluated. A total of 180 donors were excluded: 6 (0.3%) with Hepatitis B surface antigen (HBs positive), and 174 in which DNA testing was not performed. Anti-HBc was positive in 175 donors (10%), in which anti-HBs was negative in 30 (17.1%) and positive in 145 (82.9%). In total, 27 donors with DNA positive (1.5%) were found, of which 3 of 117 donors (1.7%) showed anti-HBc negative and anti-HBs positive (> 10 IU/ml), 4 of 30 donors (13.3%) showed anti-HBc positive and anti-HBs negative and 20 of 145 donors (13.8%) showed both anti-HBc and anti-HBs positive. The highest probability of finding DNA occurs when anti-HBc is positive, regardless of the presence of anti-HBs. In our study, the probability of OBI was 1.5%. The classic concept that when anti-HBc and anti-HBs are positive (even with a titer of over 100 IU/ml) the donor can be accepted should, therefore, be reconsidered, and DNA testing should be mandatory.
KeywordsTissue donors Donor selection Occult hepatitis B virus infection Multicenter study
Antibody to the Hepatitis B core antigen
Antibody to the Hepatitis B surface antigen
Hepatitis B surface antigen
Occult hepatitis B infection
The authors wish to thank Mr. Nick Shaw for his assistance with the English language version of this article.
All authors were involved in the final approval of the article submitted and are in agreement with all the content. JSI, RVM and AVS participated in the design and methodology. JSI, AVS, CRA, RVM, JCB, MPL, SFP, EVL, MJML and MGR collected data for the study. JSI and TSP performed the statistical analysis, ACC and SSO contributed to the revision and expert opinion. JSI is the author guarantor.
Compliance with ethical standards
Conflict of interest
The authors of this manuscript have no financial statement (having received no financial support for this study) or conflict of interest to disclose.
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. The study was approved by the ethics research committee of Ferrol-A Coruña (Spain), from where it was coordinated (ethical approval No. 218/342). This article does not contain any studies with animals performed by any of the authors.
- American Association of Tissue Banks (2018) AATB 2017 Annual Report. 2018. https://www.aatb.org/sites/default/files/sites/default/files/private/AATB2017AnnualReport.pdf. Accessed 2 June 2019
- Baleriola C, Johal H, Robertson P, Jacka B, Whybin R, Taylor P, Rawlinson WD (2012) Infectious disease screening of blood specimens collected post-mortem provides comparable results to pre-mortem specimens. Cell Tissue Bank 13(2):251–258. https://doi.org/10.1007/s10561-011-9252-6 CrossRefPubMedGoogle Scholar
- Colomina-Rodríguez J, González-García D, Burgos-Teruel A, Fernández-Lorenz N, Guerrero-Espejo A (2005) Significado de la reactividad aislada anti-HBc como único marcador de infección de la hepatitis B. Enfermedades Infecciosas y Microbiología Clínica 23(2):80–85. https://doi.org/10.1157/13071611 CrossRefPubMedGoogle Scholar
- Edler C, Wulff B, Schroder AS, Wilkemeyer I, Polywka S, Meyer T, Kalus U, Pruss A (2011) A prospective time-course study on serological testing for human immunodeficiency virus, hepatitis B virus and hepatitis C virus with blood samples taken up to 48 h after death. J Med Microbiol 60(Pt 7):920–926. https://doi.org/10.1099/jmm.0.027763-0 CrossRefPubMedGoogle Scholar
- Esposito A, Sabia C, Iannone C, Nicoletti GF, Sommese L, Napoli C (2017) Occult hepatitis infection in transfusion medicine: screening policy and assessment of current use of anti-HBc testing. Transfus Med Hemother 44(4):263–272. https://doi.org/10.1159/000460301 CrossRefPubMedPubMedCentralGoogle Scholar
- European Commission (2014) Summary of the 2014 annual reporting of serious adverse reactions and events for tissues and cells. https://Ec.Europa.Eu/Health/Sites/Health/Files/Blood_tissues_organs/Docs/2014_sare_summary_en.Pdf. 2014. https://ec.europa.eu/health/sites/health/files/blood_tissues_organs/docs/2014_sare_summary_en.pdf. Accessed 2 June 2019
- European Commission (2017) Summary of the 2016 annual reporting of serious adverse reactions and events for tissues and cells. https://Ec.Europa.Eu/Health/Sites/Health/Files/Blood_Tissues_Organs/Docs/2016_Sare_Tc_Summary_En.Pdf. 2017. https://ec.europa.eu/health/sites/health/files/blood_tissues_organs/docs/2016_sare_tc_summary_en.pdf. Accessed 2 June 2019
- European Directorate for the Quality of Medicine and Health Care (EDQM) (2017) Guide to the quality and safety of tissues and cells for human application, 3rd edn. Cpuncil of Europe, Strasbourg. https://www.edqm.eu/en/organs-tissues-and-cells-technical-guides
- Food and Drug Administration (2004) Eligibility determination for donors of human cells, tissues, and cellular and tissue-based products. Final rule. Fed Regist 69:29785Google Scholar
- Heim A, Wagner D, Rothämel T, Hartmann U, Flik J, Verhagen W (1999) Evaluation of serological screening of cadaveric sera for donor selection for cornea transplantation. J Med Virol 58(3):291–295. https://doi.org/10.1002/(SICI)1096-9071(199907)58:3%3c291:AID-JMV16%3e3.0.CO;2-D CrossRefPubMedGoogle Scholar
- Joint UKBTS Professional Advisory Committee (2015) Change notification UK national blood services no. 9-2015. NHS Blood and Transplant, no. 9: 5–7. https://www.transfusionguidelines.org/document-library/change-notifications/change-notifications-issues-in-2017. Accessed 2 June 2019
- Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (2017) Change notification No 34-2017 HBc Ac.Pdf.” https://Www.Transfusionguidelines.Org/Document-Library/Documents/Change-Notifcation-No-34-2017/Download-File/Change Notification 34-hepatitis B. TC.Pdf. 2017. https://www.transfusionguidelines.org/document-library/documents/change-notifcation-no-34-2017/download-file/Change notification 34-hepatitis B. TC.pdf. Accessed 2 June 2019
- Kitchen AD, Gillan HL (2010) The serological screening of deceased tissue donors within the english blood service for infectious agents: a review of current outcomes and a more effective strategy for the future. Vox Sang 98(3A):193–200. https://doi.org/10.1111/j.1423-0410.2009.01284.x CrossRefGoogle Scholar
- Launay O, Masurel J, Servant-Delmas A, Basse-Guérineau A-L, Méritet J-F, Laperche S, Sogni P, Rosenberg AR (2011) High levels of serum hepatitis B virus DNA in patients with ‘anti-HBc alone’: role of HBsAg mutants. J Viral Hepat 18(10):721–729. https://doi.org/10.1111/j.1365-2893.2011.01482.x CrossRefPubMedGoogle Scholar
- Mallick TK, Mosquera A, Zinderman CE, Martin LS, Wise RP (2012) Reported infections after human tissue transplantation before and after new Food and Drug Administration (FDA) regulations, United States, 2001 through June, 2010. Cell Tissue Bank 13(2):259–267. https://doi.org/10.1007/s10561-011-9253-5 CrossRefPubMedGoogle Scholar
- O’Brien SF, Fearon MA, Yi QL, Fan W, Scalia V, Muntz IR, Vamvakas EC (2007) Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience. Transfusion 47(10):1809–1815. https://doi.org/10.1111/j.1537-2995.2007.01396.x CrossRefPubMedGoogle Scholar
- Organizacion Nacional de Trasplantes (2018) Memoria de Donacion 2017. http://www.Ont.Es/Infesp/Memorias/Memoria%20Donaci%C3%B3n%202017.Pdf. 2018. http://www.ont.es/infesp/Memorias/MemoriaDonación2017.pdf
- Romanò L, Velati C, Cambiè G, Fomiatti L, Galli C, Zanetti AR (2013) Hepatitis B virus infection among first-time blood donors in Italy: prevalence and correlates between serological patterns and occult infection. Blood Transfus 11(2):281–288. https://doi.org/10.2450/2012.0160-12 CrossRefPubMedPubMedCentralGoogle Scholar
- Taira R, Satake M, Momose S, Hino S, Suzuki Y, Murokawa H, Uchida S, Tadokoro K (2013) Residual risk of transfusion-transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan. Transfusion 53(7):1393–1404. https://doi.org/10.1111/j.1537-2995.2012.03909.x CrossRefPubMedGoogle Scholar
- The Commission of the European Communities (2006) Commission directive 2006/17/EC of 8 February 2006 implementing directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement, and testing of human tissues and cells. Off J Eur Union 38:40–52Google Scholar
- The European Parliament and the Council of the European Union (2004) Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Off J Eur Union 102:48–58Google Scholar
- US Food and Drug (2019) Testing donors of human cells, tissues, and cellular and tissue-based products (HCT/P): specific requirements. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/testing-donors-human-cells-tissues-and-cellular-and-tissue-based-products-hctp-specific-requirements. Accessed 2 June 2019
- Van De Laar TJW, Van der Kreek TM, Molenaar-de Backer MW, Hogema BM, Zaaijer HL (2015) The yield of universal antibody to hepatitis B core antigen donor screening in the Netherlands, a hepatitis B virus low-endemic country. Transfusion 55(6):1206–1213. https://doi.org/10.1111/trf.12962 CrossRefPubMedGoogle Scholar
- Victer TN, da Fonseca C, Rodrigues S, dos Santos S, Báo N, Sampaio TL (2016) Deceased tissue donor serology and molecular testing for HIV, hepatitis B and hepatitis C viruses: a lack of cadaveric validated tests. Cell Tissue Bank 17(4):543–553. https://doi.org/10.1007/s10561-016-9564-7 CrossRefPubMedGoogle Scholar
- World Health Organization (2017) Global hepatitis report, 2017. ISBN 978-92-4-156545-5Google Scholar
- Ye X, Li T, Xiaoxuan X, Peng D, Zeng J, Zhu W, Yang B, Li C, Allain JP (2017) Characterisation and follow-up study of occult hepatitis B virus infection in anti-HBc-positive qualified blood donors in southern China. Blood Transf 15(1):6–12. https://doi.org/10.2450/2016.0268-15 CrossRefGoogle Scholar