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Bienz M, Renaud C, Liu JR, Wong P, Pelletier P. Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening? Transfus Med Rev 2024; 38:150835. [PMID: 39059853 DOI: 10.1016/j.tmrv.2024.150835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/14/2024] [Accepted: 04/17/2024] [Indexed: 07/28/2024]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
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Affiliation(s)
- Marc Bienz
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
| | - Christian Renaud
- Department of Microbiology, Infectious diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada; Medical Affairs and Innovation, Héma-Québec, Montreal, Quebec, Canada
| | - Jia Ru Liu
- Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Philip Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Patricia Pelletier
- Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada
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Niederhauser C, Gowland P, Widmer N, Amar EL Dusouqui S, Mattle-Greminger M, Gottschalk J, Frey BM. Prevalence of Acute Hepatitis E Virus Infections in Swiss Blood Donors 2018-2020. Viruses 2024; 16:744. [PMID: 38793625 PMCID: PMC11125967 DOI: 10.3390/v16050744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
INTRODUCTION Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. AIMS Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. METHODS All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available. RESULTS Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. CONCLUSION The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.
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Affiliation(s)
- Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
- Institute of Infectious Disease, University of Berne, 3008 Berne, Switzerland
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland; (P.G.)
| | | | - Maja Mattle-Greminger
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
| | - Jochen Gottschalk
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
| | - Beat M. Frey
- Regional Blood Transfusion SRC, 8952 Schlieren, Switzerland; (M.M.-G.); (J.G.); (B.M.F.)
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Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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Laperche S, Maugard C, Lhomme S, Lecam S, Ricard C, Dupont I, Richard P, Tiberghien P, Abravanel F, Morel P, Izopet J, Gallian P. Seven years (2015-2021) of blood donor screening for HEV-RNA in France: lessons and perspectives. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2023; 21:110-118. [PMID: 35969132 PMCID: PMC10072995 DOI: 10.2450/2022.0052-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 07/05/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND The French health authorities are considering expanding the current selective hepatitis E virus (HEV)-RNA testing procedure to include all donations in order to further reduce transfusion-transmitted HEV infection. Data obtained from blood donors (BDs) tested for HEV-RNA between 2015 and 2021 were used to assess the most efficient nucleic acid testing (NAT) strategy. MATERIALS AND METHODS Viral loads (VLs) and the plasma volume of blood components, as well as an HEV-RNA dose of 3.85 log IU as the infectious threshold and an assay with a 95% limit of detection (LOD) at 17 IU/mL, were used to assess the proportion of: (i) HEV-RNA-positive BDs that would remain undetected; and (ii) blood components associated with these undetected BDs with an HEV-RNA dose >3.85 log IU, considering 4 NAT options (Individual testing [ID], MP-6, MP-12, and MP-24). RESULTS Of the 510,118 BDs collected during the study period, 510 (0.10%) were HEV-RNA-positive. Based on measurable VLs available in 388 cases, 1%, 15.2%, 21.8%, and 32.6% of BDs would theoretically pass undetected due to a VL below the LOD of ID, MP-6, MP-12, and MP-24 testing, respectively. All BDs associated with a potentially infectious blood component would be detected with ID-NAT while 13% of them would be undetected with MP-6, 19.6% with MP-12, and 30.4% with MP-24 depending on the plasma volume. No red blood cell (RBC) components with an HEV-RNA dose >3.85 log IU would enter the blood supply, regardless of the NAT strategy used. DISCUSSION A highly sensitive ID-NAT would ensure maximum safety. However, an MP-based strategy can be considered given that: (i) the risk of transmission is closely related to the plasma volume of blood components; (ii) RBC are the most commonly transfused components and have a low plasma content; and (iii) HEV-RNA doses transmitting infection exceed 4 log IU. To minimise the potential risk associated with apheresis platelet components and fresh frozen plasma, less than 12 donations should be pooled using an NAT assay with a LOD of approximately 20 IU/mL.
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Affiliation(s)
- Syria Laperche
- Etablissement Français du Sang, La Plaine St-Denis, France
- Unité des Virus Émergents (UVE) Aix-Marseille-IRD 190-Inserm 1207-Marseille, France
| | - Claude Maugard
- Etablissement Français du Sang Occitanie, Montpellier, France
| | - Sébastien Lhomme
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Sophie Lecam
- Etablissement Français du Sang, La Plaine St-Denis, France
- Etablissement Français du Sang, Centre Pays de la Loire, Angers, France
| | - Céline Ricard
- Etablissement Français du Sang Hauts de France Normandie, Loos, France
| | | | | | - Pierre Tiberghien
- Etablissement Français du Sang, La Plaine St-Denis, France
- UMR 1098 RIGHT INSERM Université de Franche-Comté Etablissement Français du Sang, Besançon, France
| | - Florence Abravanel
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Pascal Morel
- Etablissement Français du Sang, La Plaine St-Denis, France
- UMR 1098 RIGHT INSERM Université de Franche-Comté Etablissement Français du Sang, Besançon, France
| | - Jacques Izopet
- Infinity, Université Toulouse III, CNRS, INSERM, Toulouse, France
- Laboratoire de Virologie, Hôpital Purpan, CHU, Toulouse, France
| | - Pierre Gallian
- Etablissement Français du Sang, La Plaine St-Denis, France
- Unité des Virus Émergents (UVE) Aix-Marseille-IRD 190-Inserm 1207-Marseille, France
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Harvala H, Reynolds C, Brailsford S, Davison K. Fulminant Transfusion-Associated Hepatitis E Virus Infection Despite Screening, England, 2016-2020. Emerg Infect Dis 2022; 28:1805-1813. [PMID: 35997399 PMCID: PMC9423923 DOI: 10.3201/eid2809.220487] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
In England, all blood donations are screened in pools of 24 by nucleic acid test (NAT) for hepatitis E virus (HEV) RNA. During 2016-2020, this screening successfully identified and intercepted 1,727 RNA-positive donations. However, review of previous donations from infected platelet donors identified 9 donations in which HEV RNA detection was missed, of which 2 resulted in confirmed transmission: 1 infection resolved with ribavirin treatment, and 1 proceeded to fatal multiorgan failure within a month from infection. Residual risk calculations predict that over the 5-year study period, HEV RNA detection was missed by minipool NAT in 12-23 platelet and 177-354 whole-blood donations, but transmission risk remains undetermined. Although screening has been able to largely eliminate infectious HEV from the blood supply in England, missed detection of low levels of HEV RNA in donated blood can lead to a severe, even fulminant, infection in recipients and could be prevented by more sensitive screening.
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Hepatitis E Virus; An Underestimated Threat for the Viral Hepatitis Elimination Program. HEPATITIS MONTHLY 2022. [DOI: 10.5812/hepatmon-129678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Mitterreiter J, Scheiblauer H, Fiedler S, Kreß J. [Safety of blood and blood products: test methods for the detection of hepatitis B, C, and E virus]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2022; 65:209-219. [PMID: 35024894 PMCID: PMC8813843 DOI: 10.1007/s00103-021-03480-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 12/10/2021] [Indexed: 11/02/2022]
Abstract
Infections with hepatitis B, C, and E virus (HBV, HCV, and HEV) can be transmitted via blood and cause severe acute or chronic liver infections. To ensure the safety of blood donations and protect recipients from virus transmissions, blood donations in Germany are tested for viral genomes using nucleic acid amplification techniques (NATs) as well as for viral antigens and antibodies by serological testing. This article describes the relevant regulations on the safety of blood and blood products in Germany and the various screening methods. The safety of blood products is assessed.Currently used NAT methods for detection of hepatitis viruses are based either on polymerase chain reaction (PCR) or isothermal methods such as transcription-mediated amplification (TMA), which enable a highly sensitive detection of viral infections and thereby contribute to the reduction of the diagnostic window. Antigen tests for the detection of viral surface protein of hepatitis B virus in blood donations were introduced in the 1970s in order to prevent potential transmissions. Since the introduction of mandatory testing for HCV-specific antibodies in 1992, HCV NAT testing in 1999, anti-HBc antibody testing in 2006, and the non-mandatory HBV NAT, which is voluntarily performed by most of the blood establishments, blood safety has increased tremendously. Only a few isolated cases of transfusion-transmitted infections in the early window period have been reported since. The success of the recent introduction of mandatory HEV NAT testing in 2020 will have to be assessed in the upcoming years. Besides blood donor screening, the system for blood safety in Germany is supplemented by additional measures for donor selection and pathogen inactivation.
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Affiliation(s)
- Johanna Mitterreiter
- Fachgebiet Molekulare Virologie, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland
| | | | - Sarah Fiedler
- Abteilung Sicherheit von Arzneimitteln und Medizinprodukten, Paul-Ehrlich-Institut, Langen, Deutschland
| | - Julia Kreß
- Fachgebiet Molekulare Virologie, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Cordes AK, Goudeva L, Lütgehetmann M, Wenzel JJ, Behrendt P, Wedemeyer H, Heim A. Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma. J Hepatol 2022; 76:46-52. [PMID: 34461207 DOI: 10.1016/j.jhep.2021.08.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/14/2022]
Abstract
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.
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Affiliation(s)
- Anne K Cordes
- Institute of Virology, Hannover Medical School, Hannover, Germany
| | - Lilia Goudeva
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Marc Lütgehetmann
- Institute of Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Patrick Behrendt
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Albert Heim
- Institute of Virology, Hannover Medical School, Hannover, Germany.
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Sakata H, Matsubayashi K, Iida J, Nakauchi K, Kishimoto S, Sato S, Ikuta K, Satake M, Kino S. Trends in hepatitis E virus infection: Analyses of the long-term screening of blood donors in Hokkaido, Japan, 2005-2019. Transfusion 2021; 61:3390-3401. [PMID: 34632593 DOI: 10.1111/trf.16700] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 08/30/2021] [Accepted: 09/23/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND After experiencing several cases of transfusion-transmitted hepatitis E (TT-HE) in Hokkaido, Northern Japan, hepatitis E virus (HEV) screening in blood donors, using a nucleic acid amplification test (NAT), was introduced in 2005. STUDY DESIGN AND METHODS The frequency of HEV RNA-positive donations (2005-2019) was investigated, and the HEV RNA-positive specimens were phylogenetically analyzed. In August 2014, the 20-pooled NAT (20P-NAT) was replaced with an individual-NAT (ID-NAT) system. RESULTS Until 2019, the frequency of HEV RNA-positive donors was 0.011% (289/2,638,685) with 20P-NAT and 0.043% (597/1,379,750) with ID-NAT, and no TT-HE cases were observed in Hokkaido. The prevalence among male, but not female donors, increased significantly between 2015 and 2019. Eighty-nine percent of HEV isolates from donors were genotype 3 and the remainder were genotype 4, and many clusters existed in each genotype. ALT levels at the time of donation were significantly higher in donors with genotype 4. Four subgenotypes, namely 3a (37%), 3b (41%), 3e (6%), and 4c (10%), comprised 94% of the total. During this period, the most identified subgenotype, 3a, transitioned to 3b. Majority of the HEV strains within the same clusters were detected in the same geographical region around the same period. Many of the human HEV isolates were shown to coexist closely with animal HEV isolates phylogenetically. CONCLUSION In Hokkaido, multiple divergent HEV strains have been circulating, and small outbreaks of hepatitis E have occurred in the last 15 years. The results suggested that HEV NAT can contribute significantly in ensuring safety during blood transfusions.
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Affiliation(s)
| | - Keiji Matsubayashi
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Juri Iida
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | - Kenta Nakauchi
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | | | - Shinichiro Sato
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
| | - Katsuya Ikuta
- Japanese Red Cross Hokkaido Blood Center, Sapporo, Japan
| | - Masahiro Satake
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Shuichi Kino
- Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan
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Platelet Transfusion-Insights from Current Practice to Future Development. J Clin Med 2021; 10:jcm10091990. [PMID: 34066360 PMCID: PMC8125287 DOI: 10.3390/jcm10091990] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/26/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022] Open
Abstract
Since the late sixties, therapeutic or prophylactic platelet transfusion has been used to relieve hemorrhagic complications of patients with, e.g., thrombocytopenia, platelet dysfunction, and injuries, and is an essential part of the supportive care in high dose chemotherapy. Current and upcoming advances will significantly affect present standards. We focus on specific issues, including the comparison of buffy-coat (BPC) and apheresis platelet concentrates (APC); plasma additive solutions (PAS); further measures for improvement of platelet storage quality; pathogen inactivation; and cold storage of platelets. The objective of this article is to give insights from current practice to future development on platelet transfusion, focusing on these selected issues, which have a potentially major impact on forthcoming guidelines.
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Praditya D, Friesland M, Gravemann U, Handke W, Todt D, Behrendt P, Müller TH, Steinmann E, Seltsam A. Hepatitis E virus is effectively inactivated in platelet concentrates by ultraviolet C light. Vox Sang 2020; 115:555-561. [PMID: 32383163 DOI: 10.1111/vox.12936] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/28/2020] [Accepted: 04/15/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES As previous investigations have shown, THERAFLEX UV-Platelets, a UVC-based pathogen inactivation (PI) system, is effective against non-enveloped transfusion-relevant viruses such as hepatitis A virus (HAV), which are insensitive to most PI treatments for blood products. This study investigated the PI efficacy of THERAFLEX UV-Platelets against HEV in platelet concentrates (PCs). MATERIALS AND METHODS Buffy coat-derived PCs in additive solution were spiked with cell culture-derived HEV and treated with the THERAFLEX UV-Platelets system using various doses of UVC (0·05, 0·10, 0·15 and 0·20 (standard) J/cm2 ). Titres of infectious virus in pre- and post-treatment samples were determined using a large-volume plating assay to improve the detection limit of the virus assay. RESULTS THERAFLEX UV-Platelets dose-dependently inactivated HEV in PCs. The standard UVC dose inactivated the virus to below the limit of detection, corresponding to a mean log reduction of greater than 3·5. CONCLUSION Our study demonstrates that the THERAFLEX UV-Platelets system effectively inactivates HEV in PCs.
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Affiliation(s)
- Dimas Praditya
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.,Research Center for Biotechnology, Indonesian Institute of Science, Cibinong, Indonesia
| | - Martina Friesland
- Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Ute Gravemann
- German Red Cross Blood Service NSTOB, Springe, Germany
| | - Wiebke Handke
- German Red Cross Blood Service NSTOB, Springe, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Patrick Behrendt
- Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.,Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.,German Centre for Infection Research, Hannover-Braunschweig, Germany
| | | | - Eike Steinmann
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Axel Seltsam
- German Red Cross Blood Service NSTOB, Springe, Germany
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13
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Transfusion-Transmitted Hepatitis E Virus Infection in France. Transfus Med Rev 2019; 33:146-153. [PMID: 31327668 DOI: 10.1016/j.tmrv.2019.06.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/27/2019] [Accepted: 06/04/2019] [Indexed: 12/14/2022]
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14
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Denner J, Pischke S, Steinmann E, Blümel J, Glebe D. Why all blood donations should be tested for hepatitis E virus (HEV). BMC Infect Dis 2019; 19:541. [PMID: 31221098 PMCID: PMC6585104 DOI: 10.1186/s12879-019-4190-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. Main text Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. Conclusion The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.
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Affiliation(s)
- Joachim Denner
- Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
| | - Sven Pischke
- 1. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
| | - Eike Steinmann
- Ruhr-Universität Bochum, Universitätsstraße 150, 44801, Bochum, Germany
| | - Johannes Blümel
- Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Schubertstr. 81, Justus-Liebig-Universität Giessen, 35392, Giessen, Germany
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Hepatitis E Virus Infection in Blood Donors and Risk to Patients in the United States and Canada. Transfus Med Rev 2019; 33:139-145. [PMID: 31324552 DOI: 10.1016/j.tmrv.2019.05.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/16/2019] [Accepted: 05/26/2019] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide including large water-borne outbreaks, zoonotic infections and transfusion transmissions. Several countries have initiated or are considering blood donor screening in response to high HEV-RNA donation prevalence leading to transfusion-transmission risk. Because HEV transmission is more common through food sources, the efficacy of blood donor screening alone may be limited. HEV-nucleic acids in 101 489 blood donations in the United States and Canada were studied. A risk-based decision-making framework was used to evaluate the quantitative risks and cost-benefit of HEV-blood donation screening in Canada comparing three scenarios: no screening, screening blood for all transfused patients or screening blood for only those at greatest risk. HEV-RNA prevalence in the United States was one per 16 908 (95% confidence interval [CI], 1:5786-1:81987), whereas Canadian HEV-RNA prevalence was one per 4615 (95% CI, 1:2579-1:9244). Although 4-fold greater, Canadian HEV-RNA prevalence was not significantly higher than in the United States. Viral loads ranged from 20 to 3080 international units per mL; all successfully typed infections were genotype 3. No HEV-RNA false-positive donations were identified for 100 percent specificity. Without donation screening, heart and lung transplant recipients had the greatest HEV-infection risk (1:366962) versus kidney transplant recipients with the lowest (1:2.8 million) at costs of $225 546 to $561 810 per quality-adjusted life-year (QALY) gained for partial or universal screening, respectively. Higher cost per QALY would be expected in the United States. Thus, HEV prevalence in North America is lower than in countries performing blood donation screening, and if implemented, is projected to be costly under any scenario.
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Lhomme S, Legrand-Abravanel F, Kamar N, Izopet J. Screening, diagnosis and risks associated with Hepatitis E virus infection. Expert Rev Anti Infect Ther 2019; 17:403-418. [DOI: 10.1080/14787210.2019.1613889] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sébastien Lhomme
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Florence Legrand-Abravanel
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Nassim Kamar
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
- Department of Nephrology and Organs Transplantation, CHU Rangueil, Toulouse, France
| | - Jacques Izopet
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
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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. [PMID: 31191195 PMCID: PMC6514502 DOI: 10.1159/000499121] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022] Open
Abstract
This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.
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Affiliation(s)
- Fiona Boland
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | | | - Louise Pomeroy
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | - Niamh O'Flaherty
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
- National Virus Reference Laboratory, University College Dublin (UCD), Dublin, Ireland
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