Cell and Tissue Banking

, Volume 20, Issue 4, pp 513–526 | Cite as

Evaluation of occult hepatitis B infection in tissue donors: a multicenter analysis in Spain

  • Jacinto Sánchez IbáñezEmail author
  • Ana Vilarrodona Serrat
  • Teresa Seoane Pillado
  • Clara Rodriguez Aierbe
  • Rafael Villalba Montoro
  • Javier Calvo Benito
  • Marta Pevida Lopez
  • Sergio Fernández Paneque
  • Elena Vuelta Lopez
  • Maria Jose Martínez Lorenzo
  • Manuel González Romero
  • Angelina Cañizares Castellanos
  • Silvia Sauleda Oliveras
Full Length Paper


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.


Tissue 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


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.

Authors contribution

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.

Ethical standards

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.


  1. Allain JP, Mihaljevic I, Gonzalez-Fraile MI, Gubbe K, Holm-Harritshøj L, Garcia JM, Brojer E et al (2013) Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion 53(7):1405–1415. CrossRefPubMedGoogle Scholar
  2. American Association of Tissue Banks (2018) AATB 2017 Annual Report. 2018. Accessed 2 June 2019
  3. Anauradha R, Garima M, Harsh B (2018) Factors affecting the serological testing of cadaveric donor cornea. Indian J Ophthalmol 66(1):61–65. CrossRefGoogle Scholar
  4. 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. CrossRefPubMedGoogle Scholar
  5. Bes M, Vargas V, Piron M, Casamitjana N, Esteban JI, Vilanova N, Pinacho A et al (2012) T cell responses and viral variability in blood donation candidates with occult hepatitis B infection. J Hepatol 56(4):765–774. CrossRefPubMedGoogle Scholar
  6. Brant LJ, Davison KL (2008) Infections detected in English surgical bone and deceased donors (2001–2006) and estimated risk of undetected hepatitis B and hepatitis C virus. Vox Sang 95(4):272–279. CrossRefPubMedGoogle Scholar
  7. Brojer E, Grabarczyk P, Liszewski G, Mikulska M, Allain JP, Letowska M, Kubicka-Russel D et al (2006) Characterization of HBV DNA+/HBsAg blood donors in Poland identified by triplex NAT. Hepatology 44(6):1666–1674. CrossRefPubMedGoogle Scholar
  8. Challine D, Roudot-Thoraval F, Sabatier P, Dubernet F, Larderie P, Rigot P, Pawlotsky JM (2006) Serological viral testing of cadaveric cornea donors. Transplantation 82(6):788–793. CrossRefPubMedGoogle Scholar
  9. Challine D, Chevaliez S, Pawlotsky JM (2008) Efficacy of serologic marker screening in identifying hepatitis B virus infection in organ, tissue, and cell donors. Gastroenterology 135(4):1185–1191. CrossRefPubMedGoogle Scholar
  10. 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. CrossRefPubMedGoogle Scholar
  11. 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. CrossRefPubMedGoogle Scholar
  12. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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. Accessed 2 June 2019
  14. 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. Accessed 2 June 2019
  15. 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.
  16. 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
  17. Fornés MG, Jiménez MA, Eisman M, Villagrán JLG, Villalba R (2016) Nucleic acid-amplification testing for hepatitis B in cornea donors. Cell Tissue Bank 17(2):341–344. CrossRefPubMedGoogle Scholar
  18. Heck E, Brown A, Cavanagh HD (2013) Nucleic acid testing and tissue safety: an eye bank’s five-year review of HIV and hepatitis testing for donor corneas. Cornea 32(4):503–505. CrossRefPubMedGoogle Scholar
  19. 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.;2-D CrossRefPubMedGoogle Scholar
  20. Hoft RH, Pflugfelder SC, Forster RK, Ullman S, Polack FM, Schiff ER (1997) Clinical evidence for hepatitis B transmission resulting from corneal transplantation. Cornea 16(2):132–137CrossRefGoogle Scholar
  21. Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, Koval C et al (2015) Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transpl 15(5):1162–1172. CrossRefGoogle Scholar
  22. Ison MG (2015) Nucleic acid testing of organ donors: Is the glass half empty or half full? Am J Transpl 15(7):1743–1745. CrossRefGoogle Scholar
  23. Joint UKBTS Professional Advisory Committee (2015) Change notification UK national blood services no. 9-2015. NHS Blood and Transplant, no. 9: 5–7. Accessed 2 June 2019
  24. 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. notification 34-hepatitis B. TC.pdf. Accessed 2 June 2019
  25. Kiely P, Margaritis AR, Seed CR, Yang H (2014) Hepatitis B virus nucleic acid amplification testing of australian blood donors highlights the complexity of confirming occult hepatitis B virus infection. Transfusion 54(8):2084–2091. CrossRefPubMedGoogle Scholar
  26. 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. CrossRefGoogle Scholar
  27. Kitchen AD, Newham JA, Gillan HL (2013) Effective serological and molecular screening of deceased tissue donors. Cell Tissue Bank 14(4):633–644. CrossRefPubMedGoogle Scholar
  28. Kurt Roth W, Schuller A, Busch MP, Reesink HW, Panzer S (2012) International survey on NAT testing of blood donations: expanding implementation and yield from 1999 to 2009. Vox Sang 102(1):82–90. CrossRefGoogle Scholar
  29. 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. CrossRefPubMedGoogle Scholar
  30. Levicnik-Stezinar S, Rahne-Potokar U, Candotti D, Lelie N, Allain JP (2008) Anti-HBs positive occult hepatitis B virus carrier blood infectious in two transfusion recipients. J Hepatol 48(6):1022–1025. CrossRefPubMedGoogle Scholar
  31. 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. CrossRefPubMedGoogle Scholar
  32. Manzini P, Girotto M, Borsotti R, Giachino O, Guaschino R, Lanteri M, Testa D et al (2007) Italian blood donors with anti-HBc and occult hepatitis B virus infection. Haematologica 92(12):1664–1670. CrossRefPubMedGoogle Scholar
  33. Migden MR, Dennis WH, Clinch TE (1996) Testing for hepatitis B surface antigen in processing donor tissue for penetrating keratoplasty. Am J Ophthalmol 122(3):439–442. CrossRefPubMedGoogle Scholar
  34. Mirabet V, Álvarez M, Luis-Hidalgo M, Galán J, Puig N, Larrea L, Arbona C (2017) Detection of hepatitis B virus in bone allografts from donors with occult hepatitis B infection. Cell Tissue Bank 18(3):335–341. CrossRefPubMedGoogle Scholar
  35. Morris A, Strickett MG, Barratt-Boyes BG (1990) Use of aortic valve allografts from hepatitis B surface antigen-positive donors. Ann Thorac Surg 49(5):802–805. CrossRefPubMedGoogle Scholar
  36. 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. CrossRefPubMedGoogle Scholar
  37. Pruss A, Caspari G, Krüger DH, Blümel J, Nübling CM, Gürtler L, Gerlich WH (2010) Tissue donation and virus safety: more nucleic acid amplification testing is needed. Transpl Infect Dis 12(5):375–386. CrossRefPubMedGoogle Scholar
  38. Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS (2019) Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. CrossRefPubMedGoogle Scholar
  39. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Seo DH, Whang DH, Song EY, Han KS (2015) Occult hepatitis B virus infection and blood transfusion. World J Hepatol 7(3):600–606. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Shutkin NM (1954) Homologous-serum hepatitis following the use of refrigerated bone-bank bone. J Bone Joint Surg Am 36(1):160–162CrossRefGoogle Scholar
  42. Solves P, Mirabet V, Alvarez M (2014) Hepatitis B transmission by cell and tissue allografts: How safe is safe enough? World J Gastroenterol 20(23):7434–7441. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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. CrossRefPubMedGoogle Scholar
  44. 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
  45. 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
  46. Theodoropoulos N, Jaramillo A, Ladner DP, Ison MG (2013) Deceased organ donor screening for HIV, hepatitis B, and hepatitis C viruses: a survey of organ procurement organization practices. Am J Transpl 13(8):2186–2190. CrossRefGoogle Scholar
  47. Thijssen EricJM, Kroes AloysCM, Bos E, Persijn GG, Rothbarth PH (1993) The significance of complete serological testing for hepatitis B in heart valve banking. Transplantation 56:82–84. CrossRefPubMedGoogle Scholar
  48. US Food and Drug (2019) Testing donors of human cells, tissues, and cellular and tissue-based products (HCT/P): specific requirements. Accessed 2 June 2019
  49. 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. CrossRefPubMedGoogle Scholar
  50. 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. CrossRefPubMedGoogle Scholar
  51. Villalba R, Fornés G, Eisman M, Villagrán JLG (2007) Evaluation of tissue discards after implementation of anti-HBc test in a tissue bank in Spain. Cell Tissue Bank 8:303–305. CrossRefPubMedGoogle Scholar
  52. Weber B, Melchior W, Gehrke R, Doerr HW, Berger A, Rabenau H (2001) Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virol 64(3):312–319. CrossRefPubMedGoogle Scholar
  53. Wilkemeyer I, Pruss A, Kalus U, Schroeter J (2012) Comparative infectious serology testing of pre- and postmortem blood samples from cornea donors. Cell Tissue Bank 13(3):447–452. CrossRefPubMedGoogle Scholar
  54. World Health Organization (2017) Global hepatitis report, 2017. ISBN 978-92-4-156545-5Google Scholar
  55. Yao F, Seed C, Farrugia A, Morgan D, Cordner S, Wood D, Zheng MH (2007) The risk of HIV, HBV, HCV and HTLV infection among musculoskeletal tissue donors in Australia. Am J Transpl 7(12):2723–2726. CrossRefGoogle Scholar
  56. 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. CrossRefGoogle Scholar
  57. Zou S, Dodd RY, Stramer SL, Michael Strong D (2004) Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States. N Engl J Med 351(8):751–759. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Cryobiology Unit – Tissue Establishment, Complejo Hospitalario Universitario de A CoruñaA Coruña University HospitalA CoruñaSpain
  2. 2.Tissue EstablishmentBanc de Sang i TeixitsBarcelonaSpain
  3. 3.Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigacion Biomedica de A CoruñaA Coruña University HospitalA CoruñaSpain
  4. 4.Tissue EstablishmentCentro Vasco de Transfusión y Tejidos HumanosGaldakaoSpain
  5. 5.Tissue EstablishmentCentro de Transfusión de Tejidos y CélulasCórdobaSpain
  6. 6.Tissue Establishment, Balearic Island Blood and Tissue Bank Foundation (FBSTIB), Cell Therapy and Tissue Engineering Group (TERCIT)Balearic Islands Institute of Health Research (IdISBa)Palma de MallorcaSpain
  7. 7.Tissue EstablishmentCentro Comunitario de Sangre y Tejidos del Principado de AsturiasOviedoSpain
  8. 8.Tissue EstablishmentCentro de Transfusión, Tejidos y CélulasMálagaSpain
  9. 9.Tissue EstablishmentEstablecimiento de Tejidos Humanos, Fundación Clinica San FranciscoLeónSpain
  10. 10.Tissue EstablishmentBanco de Sangre y Tejidos de AragónSaragossaSpain
  11. 11.Tissue EstablishmentHospital Clínico San CarlosMadridSpain
  12. 12.Microbiology DepartmentA Coruña University HospitalA CoruñaSpain
  13. 13.Transfusion Safety LaboratoryBanc de Sang I TeixitsBarcelonaSpain

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