Research article Open Access
Like 0


Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in developed countries, which seems partly due to differences in assay sensitivity. Using validated sensitive assays, we tested 313 blood donors attending a hospital transfusion unit in central Italy in January and February 2014 for anti-HEV IgG and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was the only independent predictor of HEV infection (adjusted prevalence rate ratio = 2.14; 95% confidence interval: 1.23–3.74). Three donors were positive for either anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is therefore hyperendemic among blood donors (80% men 18–64 years-old) from central Italy and associated with local dietary habits. Nearly 1% of donors have acute or recent infection, implying potential transmission to blood recipients. Neither ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV infection.


Article metrics loading...

Loading full text...

Full text loading...



  1. Aggarwal R, Jameel S. Hepatitis E. Hepatology. 2011;54(6):2218-26.  https://doi.org/10.1002/hep.24674  PMID: 21932388 
  2. Kamar N, Dalton HR, Abravanel F, Izopet J. Hepatitis E virus infection. Clin Microbiol Rev. 2014;27(1):116-38.  https://doi.org/10.1128/CMR.00057-13  PMID: 24396139 
  3. Fujiwara S, Yokokawa Y, Morino K, Hayasaka K, Kawabata M, Shimizu T. Chronic hepatitis E: a review of the literature. J Viral Hepat. 2014;21(2):78-89.  https://doi.org/10.1111/jvh.12156  PMID: 24383921 
  4. Bazerbachi F, Haffar S, Garg SK, Lake JR. Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. Gastroenterol Rep (Oxf). 2015;4(1):1-15.  https://doi.org/10.1093/gastro/gov042  PMID: 26358655 
  5. Fogeda M, Avellón A, Echevarría JM. Prevalence of specific antibody to hepatitis E virus in the general population of the community of Madrid, Spain. J Med Virol. 2012;84(1):71-4.  https://doi.org/10.1002/jmv.22270  PMID: 22095537 
  6. Faber MS, Wenzel JJ, Jilg W, Thamm M, Höhle M, Stark K. Hepatitis E virus seroprevalence among adults, Germany. Emerg Infect Dis. 2012;18(10):1654-7.  https://doi.org/10.3201/eid1810.111756  PMID: 23018055 
  7. Ijaz S, Vyse AJ, Morgan D, Pebody RG, Tedder RS, Brown D. Indigenous hepatitis E virus infection in England: more common than it seems. J Clin Virol. 2009;44(4):272-6.  https://doi.org/10.1016/j.jcv.2009.01.005  PMID: 19217345 
  8. Verhoef L, Koopmans M, Duizer E, Bakker J, Reimerink J, Van Pelt W. Seroprevalence of hepatitis E antibodies and risk profile of HEV seropositivity in The Netherlands, 2006-2007. Epidemiol Infect. 2012;140(10):1838-47.  https://doi.org/10.1017/S0950268811002913  PMID: 22269886 
  9. Wenzel JJ, Sichler M, Schemmerer M, Behrens G, Leitzmann MF, Jilg W. Decline in hepatitis E virus antibody prevalence in southeastern Germany, 1996-2011. Hepatology. 2014;60(4):1180-6.  https://doi.org/10.1002/hep.27244  PMID: 24912687 
  10. Dreier J, Juhl D. Autochthonous hepatitis e virus infections: a new transfusion-associated risk? Transfus Med Hemother. 2014;41(1):29-39.  https://doi.org/10.1159/000357098  PMID: 24659945 
  11. Mansuy JM, Bendall R, Legrand-Abravanel F, Sauné K, Miédouge M, Ellis V, et al. Hepatitis E virus antibodies in blood donors, France. Emerg Infect Dis. 2011;17(12):2309-12.  https://doi.org/10.3201/eid1712.110371  PMID: 22172156 
  12. Cleland A, Smith L, Crossan C, Blatchford O, Dalton HR, Scobie L, et al. Hepatitis E virus in Scottish blood donors. Vox Sang. 2013;105(4):283-9.  https://doi.org/10.1111/vox.12056  PMID: 23763589 
  13. Juhl D, Baylis SA, Blümel J, Görg S, Hennig H. Seroprevalence and incidence of hepatitis E virus infection in German blood donors. Transfusion. 2014;54(1):49-56.  https://doi.org/10.1111/trf.12121  PMID: 23441647 
  14. Kaufmann A, Kenfak-Foguena A, André C, Canellini G, Bürgisser P, Moradpour D, et al. Hepatitis E virus seroprevalence among blood donors in southwest Switzerland. PLoS One. 2011;6(6):e21150.  https://doi.org/10.1371/journal.pone.0021150  PMID: 21701586 
  15. Beale MA, Tettmar K, Szypulska R, Tedder RS, Ijaz S. Is there evidence of recent hepatitis E virus infection in English and North Welsh blood donors? Vox Sang. 2011;100(3):340-2.  https://doi.org/10.1111/j.1423-0410.2010.01412.x  PMID: 21392024 
  16. Sauleda S, Ong E, Bes M, Janssen A, Cory R, Babizki M, et al. Seroprevalence of hepatitis E virus (HEV) and detection of HEV RNA with a transcription-mediated amplification assay in blood donors from Catalonia (Spain). Transfusion. 2015;55(5):972-9.  https://doi.org/10.1111/trf.12929  PMID: 25403913 
  17. Fischer C, Hofmann M, Danzer M, Hofer K, Kaar J, Gabriel C. Seroprevalence and Incidence of hepatitis E in blood donors in Upper Austria. PLoS One. 2015;10(3):e0119576.  https://doi.org/10.1371/journal.pone.0119576  PMID: 25751574 
  18. Holm DK, Moessner BK, Engle RE, Zaaijer HL, Georgsen J, Purcell RH, et al. Declining prevalence of hepatitis E antibodies among Danish blood donors. Transfusion. 2015;55(7):1662-7.  https://doi.org/10.1111/trf.13028  PMID: 25819381 
  19. Zanetti AR, Dawson GJ. Hepatitis type E in Italy: A seroepidemiological survey. J Med Virol. 1994;42(3):318-20.  https://doi.org/10.1002/jmv.1890420321  PMID: 8006645 
  20. Vulcano A, Angelucci M, Candelori E, Martini V, Patti AM, Mancini C, et al. HEV prevalence in the general population and among workers at zoonotic risk in Latium Region. Ann Ig. 2007;19(3):181-6. PMID: 17658105 
  21. Masia G, Orrù G, Liciardi M, Desogus G, Coppola RC, Murru V, et al. Evidence of hepatitis E virus (HEV) infection in human and pigs in Sardinia, Italy. J Prev Med Hyg. 2009;50(4):227-31. PMID: 20812518 
  22. Scotto G, Martinelli D, Centra M, Querques M, Vittorio F, Delli Carri P, et al. Epidemiological and clinical features of HEV infection: a survey in the district of Foggia (Apulia, Southern Italy). Epidemiol Infect. 2014;142(2):287-94.  https://doi.org/10.1017/S0950268813001167  PMID: 23673019 
  23. Puttini C, Riccio ML, Redi D, Tordini G, Cenerini M, Romanello F, et al. Seroprevalence of hepatitis E virus (HEV) infection in blood donors and renal transplant recipients: a retrospective study from central Italy. Infez Med. 2015;23(3):253-6. PMID: 26397295 
  24. Mansuy JM, Saune K, Rech H, Abravanel F, Mengelle C, L’Homme S, et al. L Homme S, Destruel F, Kamar N, Izopet J: Seroprevalence in blood donors reveals widespread, multi-source exposure to hepatitis E virus, southern France, October 2011. Euro Surveill. 2015;20(19):21127.  https://doi.org/10.2807/1560-7917.ES2015.20.19.21127  PMID: 25990359 
  25. Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, et al. Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus Med. 2006;16(2):79-83.  https://doi.org/10.1111/j.1365-3148.2006.00652.x  PMID: 16623913 
  26. Colson P, Coze C, Gallian P, Henry M, De Micco P, Tamalet C. Transfusion-associated hepatitis E, France. Emerg Infect Dis. 2007;13(4):648-9.  https://doi.org/10.3201/eid1304.061387  PMID: 17561564 
  27. Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion. 2008;48(7):1368-75.  https://doi.org/10.1111/j.1537-2995.2008.01722.x  PMID: 18651907 
  28. La Rosa G, Fratini M, Muscillo M, Iaconelli M, Taffon S, Equestre M, et al. Molecular characterisation of human hepatitis E virus from Italy: comparative analysis of five reverse transcription-PCR assays. Virol J. 2014;11(1):72.  https://doi.org/10.1186/1743-422X-11-72  PMID: 24755361 
  29. Barnaud E, Rogée S, Garry P, Rose N, Pavio N. Thermal inactivation of infectious hepatitis E virus in experimentally contaminated food. Appl Environ Microbiol. 2012;78(15):5153-9.  https://doi.org/10.1128/AEM.00436-12  PMID: 22610436 
  30. Hosmer DW LS: Applied logistic regression New York, 1989.
  31. Bendall R, Ellis V, Ijaz S, Ali R, Dalton H. A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries. J Med Virol. 2010;82(5):799-805.  https://doi.org/10.1002/jmv.21656  PMID: 20336757 
  32. Wenzel JJ, Preiss J, Schemmerer M, Huber B, Jilg W. Test performance characteristics of Anti-HEV IgG assays strongly influence hepatitis E seroprevalence estimates. J Infect Dis. 2013;207(3):497-500.  https://doi.org/10.1093/infdis/jis688  PMID: 23148290 
  33. Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W, et al. Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur J Gastroenterol Hepatol. 2008;20(8):784-90.  https://doi.org/10.1097/MEG.0b013e3282f5195a  PMID: 18617784 
  34. Slot E, Hogema BM, Riezebos-Brilman A, Kok TM, Molier M, Zaaijer HL. Silent hepatitis E virus infection in Dutch blood donors, 2011 to 2012. Euro Surveill. 2013;18(31):20550.  https://doi.org/10.2807/1560-7917.ES2013.18.31.20550  PMID: 23929229 
  35. Colson P, Borentain P, Queyriaux B, Kaba M, Moal V, Gallian P, et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis. 2010;202(6):825-34.  https://doi.org/10.1086/655898  PMID: 20695796 
  36. Legrand-Abravanel F, Kamar N, Sandres-Saune K, Garrouste C, Dubois M, Mansuy JM, et al. Characteristics of autochthonous hepatitis E virus infection in solid-organ transplant recipients in France. J Infect Dis. 2010;202(6):835-44.  https://doi.org/10.1086/655899  PMID: 20695798 
  37. Wichmann O, Schimanski S, Koch J, Kohler M, Rothe C, Plentz A, et al. Phylogenetic and case-control study on hepatitis E virus infection in Germany. J Infect Dis. 2008;198(12):1732-41.  https://doi.org/10.1086/593211  PMID: 18983248 
  38. Di Bartolo I, Martelli F, Inglese N, Pourshaban M, Caprioli A, Ostanello F, et al. Widespread diffusion of genotype 3 hepatitis E virus among farming swine in Northern Italy. Vet Microbiol. 2008;132(1-2):47-55.  https://doi.org/10.1016/j.vetmic.2008.04.028  PMID: 18538512 
  39. Di Bartolo I, Ponterio E, Castellini L, Ostanello F, Ruggeri FM. Viral and antibody HEV prevalence in swine at slaughterhouse in Italy. Vet Microbiol. 2011;149(3-4):330-8.  https://doi.org/10.1016/j.vetmic.2010.12.007  PMID: 21216541 
  40. Di Bartolo I, Angeloni G, Ponterio E, Ostanello F, Ruggeri FM. Detection of hepatitis E virus in pork liver sausages. Int J Food Microbiol. 2015;193:29-33.  https://doi.org/10.1016/j.ijfoodmicro.2014.10.005  PMID: 25462920 
  41. Di Bartolo I, Diez-Valcarce M, Vasickova P, Kralik P, Hernandez M, Angeloni G, et al. Hepatitis E virus in pork production chain in Czech Republic, Italy, and Spain, 2010. Emerg Infect Dis. 2012;18(8):1282-9.  https://doi.org/10.3201/eid1808.111783  PMID: 22840221 
  42. Vollmer T, Diekmann J, Johne R, Eberhardt M, Knabbe C, Dreier J. Novel approach for detection of hepatitis E virus infection in German blood donors. J Clin Microbiol. 2012;50(8):2708-13.  https://doi.org/10.1128/JCM.01119-12  PMID: 22675127 
  43. Gallian P, Lhomme S, Piquet Y, Sauné K, Abravanel F, Assal A, et al. Hepatitis E virus infections in blood donors, France. Emerg Infect Dis. 2014;20(11):1914-7.  https://doi.org/10.3201/eid2011.140516  PMID: 25340881 
  44. Hewitt PE, Ijaz S, Brailsford SR, Brett R, Dicks S, Haywood B, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014;384(9956):1766-73.  https://doi.org/10.1016/S0140-6736(14)61034-5  PMID: 25078306 
  45. Epicentro. Il portale dell'epidemiologia per la sanità pubblica. Epatite virale. Aspetti epidemiologici. In Italia. [Viral hepatitis. Epidemiological aspects. In Italy]. Roma: Istituto superiore di sanità; 2015. Available from: http://www.Epicentro.Iss.It/problemi/epatite/epidemiologiaitalia.Asp
  46. Stroffolini T, Menchinelli M, Dambruoso V, Menniti Ippolito F, Costantino A, Rapicetta M, et al. Prevalence of hepatitis E in a central Italian town at high endemicity for hepatitis C virus. Ital J Gastroenterol. 1996;28(9):523-5. PMID: 9131399 
  47. Gessoni G, Manoni F. Hepatitis E virus infection in north-east Italy: serological study in the open population and groups at risk. J Viral Hepat. 1996;3(4):197-202.  https://doi.org/10.1111/j.1365-2893.1996.tb00095.x  PMID: 8871881 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error