Advertisement

Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma

Published:August 27, 2021DOI:https://doi.org/10.1016/j.jhep.2021.08.018

      Highlights

      • HEV can be transmitted in spite of pool testing of blood donors for HEV RNA.
      • APCs and FFP are associated with a higher risk of transmitting HEV than RCCs.
      • Pooled BD testing insufficiently reduces the risk of tt HEV when giving APC and FFP donations.
      • Single donor testing for HEV RNA should significantly increase the safety of blood products.

      Background and Aims

      Immunocompromised patients are at risk of chronic hepatitis E which can be acquired by blood transfusions. Currently, screening of blood donors (BDs) for HEV RNA with a limit of detection (LOD) of 2,000 IU/ml is required in Germany. However, this may result in up to 440,000 IU of HEV RNA in blood products depending on their plasma volume. We studied the residual risk of transfusion-transmitted (tt) HEV infection when an LOD of 2,000 IU/ml is applied.

      Methods

      Highly sensitive individual donor testing for HEV RNA on the Grifols Procleix Panther system (LOD 7.89 IU/ml) was performed. HEV loads were quantified by real-time PCR.

      Results

      Of 16,236 donors, 31 (0.19%) were HEV RNA positive. Three BDs had viral loads between 710 and 2,000 IU/ml, which pose a significant risk of tt hepatitis E with any type of blood product. Eight BDs had viral loads of >32 to 710 IU/ml, which pose a risk of tt hepatitis E with platelet or plasma transfusions because of their higher plasma volume compared to red blood cell concentrates. Eight of these 11 potentially infectious BDs were seronegative for HEV, indicating a recent infection. Only 8 of 31 donors had viral loads >2,000 IU/ml that would also have been detected by the required screening procedure and 12 had very low HEV loads (<32 IU/ml).

      Conclusions

      Screening of BDs with an LOD of 2,000 IU/ml reduced the risk of tt HEV infection by about 73% for red blood cell concentrates but by just 42% for platelet and fresh frozen plasma transfusions. Single donor screening (LOD <32 IU/ml) should lead to an almost 100% risk reduction.

      Lay summary

      Immunocompromised patients, such as solid organ or hematopoietic stem cell recipients, are at risk of chronic hepatitis E, which can be acquired via blood transfusions. The risk of transfusion-transmitted hepatitis E in these patients may not be sufficiently controlled by (mini-)pool hepatitis E virus RNA screening of blood donors. Single donor screening should be considered to improve the safety of blood products.

      Graphical abstract

      Keywords

      Linked Article

      • Identification of rabbit hepatitis E virus (HEV) and novel HEV clade in Irish blood donors
        Journal of HepatologyVol. 77Issue 3
        • Preview
          We read with interest that Cordes et al.1 undertook a study wherein they performed individual donor nucleic acid testing (ID-NAT) for hepatitis E virus (HEV) in Germany using the Procleix HEV assay (Grifols, Barcelona, Spain). Using a similar approach, between January 4th, 2016 and March 17th, 2017, 172,277 blood donations were screened for HEV by the Irish Blood Transfusion Service. Screening was performed by ID-NAT using the Procleix HEV assay on the automated Procleix Panther System (Grifols).
        • Full-Text
        • PDF
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lozano R.
        • Naghavi M.
        • Foreman K.
        • Lim S.
        • Shibuya K.
        • Aboyans V.
        • et al.
        Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
        Lancet. 2012; 380: 2095-2128
        • Hoofnagle J.H.
        • Nelson K.E.
        • Purcell R.H.
        Hepatitis E.
        N Engl J Med. 2012; 367: 1237-1244
        • Mansuy J.M.
        • Gallian P.
        • Dimeglio C.
        • Saune K.
        • Arnaud C.
        • Pelletier B.
        • et al.
        A nationwide survey of hepatitis E viral infection in French blood donors.
        Hepatology. 2016; 63: 1145-1154
        • von Felden J.
        • Alric L.
        • Pischke S.
        • Aitken C.
        • Schlabe S.
        • Spengler U.
        • et al.
        The burden of hepatitis E among patients with haematological malignancies: a retrospective European cohort study.
        J Hepatol. 2019; 71: 465-472
        • 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: 79-83
        • Gallian P.
        • Pouchol E.
        • Djoudi R.
        • Lhomme S.
        • Mouna L.
        • Gross S.
        • et al.
        Transfusion-transmitted hepatitis E virus infection in France.
        Transfus Med Rev. 2019; 33: 146-153
        • Hewitt P.E.
        • Ijaz S.
        • Brailsford S.R.
        • 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: 1766-1773
        • Himmelsbach K.
        • Bender D.
        • Hildt E.
        Life cycle and morphogenesis of the hepatitis E virus.
        Emerg Microbes Infect. 2018; 7: 196
        • Dreier J.
        • Knabbe C.
        • Vollmer T.
        Transfusion-transmitted hepatitis E: NAT screening of blood donations and infectious dose.
        Front Med (Lausanne). 2018; 5: 5
        • Tedder R.S.
        • Ijaz S.
        • Kitchen A.
        • Ushiro-Lumb I.
        • Tettmar K.I.
        • Hewitt P.
        • et al.
        Hepatitis E risks: pigs or blood-that is the question.
        Transfusion. 2017; 57: 267-272
        • Boland F.
        • Martinez A.
        • Pomeroy L.
        • O'Flaherty N.
        Blood donor screening for hepatitis E virus in the European union.
        Transfus Med Hemother. 2019; 46: 95-103
        • Kamp C.
        • Blümel J.
        • Baylis S.A.
        • Bekeredjian-Ding I.
        • Chudy M.
        • Heiden M.
        • et al.
        Impact of hepatitis E virus testing on the safety of blood components in Germany - results of a simulation study.
        Vox Sang. 2018; 113: 811-813
      1. Grifols. Procleix UltrioPlex E assay. 2021 ([cited 2021 23.04.2021]; Available from:)
        • Allweiss L.
        • Gass S.
        • Giersch K.
        • Groth A.
        • Kah J.
        • Volz T.
        • et al.
        Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation.
        J Hepatol. 2016; 64: 1033-1040
        • Wenzel J.J.
        • Preiss J.
        • Schemmerer M.
        • Huber B.
        • Plentz A.
        • Jilg W.
        Detection of hepatitis E virus (HEV) from porcine livers in Southeastern Germany and high sequence homology to human HEV isolates.
        J Clin Virol. 2011; 52: 50-54
        • Mulder A.C.
        • Kroneman A.
        • Franz E.
        • Vennema H.
        • Tulen A.D.
        • Takkinen J.
        • et al.
        HEVnet: a One Health, collaborative, interdisciplinary network and sequence data repository for enhanced hepatitis E virus molecular typing, characterisation and epidemiological investigations.
        Euro Surveill. 2019; 24
        • Edgar R.C.
        MUSCLE: multiple sequence alignment with high accuracy and high throughput.
        Nucleic Acids Res. 2004; 32: 1792-1797
        • Stamatakis A.
        RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies.
        Bioinformatics. 2014; 30: 1312-1313
        • Smith D.B.
        • Izopet J.
        • Nicot F.
        • Simmonds P.
        • Jameel S.
        • Meng X.J.
        • et al.
        Update: proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A).
        J Gen Virol. 2020; 101: 692-698
        • Wantai
        Wantai HEV ELISA assays.
        2021 ([cited 13.07.2021]; Available from:)
        • Vollmer T.
        • Diekmann J.
        • Knabbe C.
        • Dreier J.
        Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed?.
        Transfusion. 2019; 59: 612-622
        • Faber M.S.
        • Wenzel J.J.
        • Jilg W.
        • Thamm M.
        • Höhle M.
        • Stark K.
        Hepatitis E virus seroprevalence among adults, Germany.
        Emerg Infect Dis. 2012; 18: 1654-1657
        • Ankcorn M.
        • Moreira F.
        • Ijaz S.
        • Symes A.
        • Buckland M.S.
        • Workman S.
        • et al.
        Absence of persistent hepatitis E virus infection in antibody-deficient patients is associated with transfer of antigen-neutralizing antibodies from immunoglobulin products.
        J Infect Dis. 2019; 219: 245-253
        • Pischke S.
        • Horn-Wichmann R.
        • Ernst D.
        • Meyer B.G.
        • Raupach R.
        • Ahrenstorf G.
        • et al.
        Absence of chronic hepatitis E in a German cohort of common variable immunodeficiency patients.
        Infect Dis Rep. 2012; 4: e28
        • Nagashima S.
        • Takahashi M.
        • Kobayashi T.
        • Nishizawa T.
        • Nishiyama T.
        • Primadharsini P.P.
        • et al.
        Characterization of the quasi-enveloped hepatitis E virus particles released by the cellular exosomal pathway.
        J Virol. 2017; 91
        • Chapuy-Regaud S.
        • Dubois M.
        • Plisson-Chastang C.
        • Bonnefois T.
        • Lhomme S.
        • Bertrand-Michel J.
        • et al.
        Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response.
        Biochimie. 2017; 141: 70-79
        • Pallerla S.R.
        • Schembecker S.
        • Meyer C.G.
        • Linh L.T.K.
        • Johne R.
        • Wedemeyer H.
        • et al.
        Hepatitis E virus genome detection in commercial pork livers and pork meat products in Germany.
        J Viral Hepat. 2021; 28: 196-204
        • Koch F.
        • Heuer T.
        • Krems C.
        • Claupein E.
        Meat consumers and non-meat consumers in Germany: a characterisation based on results of the German National Nutrition Survey II.
        J Nutr Sci. 2019; 8: e21
        • Slot E.
        • Zaaijer H.L.
        • Molier M.
        • Van den Hurk K.
        • Prinsze F.
        • Hogema B.M.
        Meat consumption is a major risk factor for hepatitis E virus infection.
        PloS One. 2017; 12e0176414
        • Sahli R.
        • Fraga M.
        • Semela D.
        • Moradpour D.
        • Gouttenoire J.
        Rabbit HEV in immunosuppressed patients with hepatitis E acquired in Switzerland.
        J Hepatol. 2019; 70: 1023-1025
        • Abravanel F.
        • Lhomme S.
        • El Costa H.
        • Schvartz B.
        • Peron J.M.
        • Kamar N.
        • et al.
        Rabbit hepatitis E virus infections in humans, France.
        Emerg Infect Dis. 2017; 23: 1191-1193
        • Ryll R.
        • Eiden M.
        • Heuser E.
        • Weinhardt M.
        • Ziege M.
        • Höper D.
        • et al.
        Hepatitis E virus in feral rabbits along a rural-urban transect in Central Germany.
        Infect Genet Evol. 2018; 61: 155-159
        • Vollmer T.
        • Diekmann J.
        • Eberhardt M.
        • Knabbe C.
        • Dreier J.
        Hepatitis E in blood donors: investigation of the natural course of asymptomatic infection, Germany, 2011.
        Euro Surveill. 2016; : 21