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Kanda T, Okamoto H. Thermal Inactivation of Hepatitis E Virus: A Narrative Review. Viruses 2025; 17:702. [PMID: 40431713 PMCID: PMC12115974 DOI: 10.3390/v17050702] [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: 04/14/2025] [Revised: 05/12/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Hepatitis E virus (HEV) infection is an emerging infectious disease. HEV-1 and HEV-2 infect humans through contaminated water and foods, mainly in developing countries. HEV-3 and HEV-4 also infect humans through contaminated food and are thought to be zoonotic infections occurring in both developing and developed countries. A vaccine for hepatitis E is licensed in only limited countries. The inactivation of infectious HEV is very important to ensure the safety of drinking water and foods. HEV-3 and HEV-4 RNA have been detected in some pig liver products, and it is possible that these foods may represent an infectious source of HEV. In this article, previous publications on the heat inactivation and heat stability of HEV are collected, and we discuss the present assessment of the heat inactivation of HEV. The thermal stability of HEV infection in cell culture systems and pig bioassays has been demonstrated, while the efficacy of the method of thermal inactivation using plasma products has not yet been established. Here, we propose that the treatment of HEV-contaminated foods at 95 °C for 10 min is one of the safest options for the inactivation of HEV.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Uonuma Kikan Hospital, Minami-Uonuma 949-7302, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-shi 329-0498, Tochigi, Japan;
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Flegel WA. Pathogen-reduction technology, good in more than one way for cellular blood components, is replacing irradiation. Transfus Apher Sci 2025; 64:104088. [PMID: 39947047 PMCID: PMC11979863 DOI: 10.1016/j.transci.2025.104088] [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] [Indexed: 03/05/2025]
Abstract
Clinical application of pathogen-reduction technology (PRT) is often restricted to platelet and non-cellular components, representing a minor fraction of the overall blood supply. The greatest benefit for patient safety may eventually derive from PRT in red cells, which is still unavailable for routine use. PRT is more effective to inactivate leukocytes than current irradiation, particularly pertinent for Japan with the only universal irradiation of cellular blood components. Elsewhere, only vulnerable patient cohorts are receiving irradiated cellular components. Blood components treated with approved PRT systems are exempt from irradiation if the patient requires irradiated components. Transfusion medicine has a strategic opportunity to develop and eventually utilize PRT for all cellular components, other than hematopoietic progenitor cell products. PRT would then enable leukocyte inactivation for 100 % of the blood supply, beneficial for transfusion safety in all patients.
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Affiliation(s)
- Willy Albert Flegel
- Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA; Department of Pathology, Georgetown University Medical Center, Washington, DC, USA.
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Piccin A, Allameddine A, Spizzo G, Lappin KM, Prati D. Platelet Pathogen Reduction Technology-Should We Stay or Should We Go…? J Clin Med 2024; 13:5359. [PMID: 39336845 PMCID: PMC11432127 DOI: 10.3390/jcm13185359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/16/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
The recent COVID-19 pandemic has significantly challenged blood transfusion services (BTS) for providing blood products and for keeping blood supplies available. The possibility that a similar pandemic event may occur again has induced researchers and transfusionists to investigate the adoption of new tools to prevent and reduce these risks. Similarly, increased donor travelling and globalization, with consequent donor deferral and donor pool reduction, have contributed to raising awareness on this topic. Although recent studies have validated the use of pathogen reduction technology (PRT) for the control of transfusion-transmitted infections (TTI) this method is not a standard of care despite increasing adoption. We present a critical commentary on the role of PRT for platelets and on associated problems for blood transfusion services (BTS). The balance of the cost effectiveness of adopting PRT is also discussed.
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Affiliation(s)
- Andrea Piccin
- Northern Ireland Blood Transfusion Service (NIBTS), Belfast BT9 7TS, UK
- Department of Internal Medicine V, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Department of Industrial Engineering, University of Trento, 38122 Trento, Italy
| | | | - Gilbert Spizzo
- Department of Oncology, Brixen Hospital, 39042 Bolzano, Italy
| | - Katrina M Lappin
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT7 1NN, UK
| | - Daniele Prati
- Servizio Trasfusionale, Ospedale Ca' Granda, 20122 Milano, Italy
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Kanda T, Li TC, Takahashi M, Nagashima S, Primadharsini PP, Kunita S, Sasaki-Tanaka R, Inoue J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K, Yokosuka O, Suzuki R, Ishii K, Yotsuyanagi H, Okamoto H. Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection. Hepatol Res 2024; 54:1-30. [PMID: 38874115 DOI: 10.1111/hepr.14062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/22/2024] [Accepted: 05/09/2024] [Indexed: 06/15/2024]
Abstract
Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Satoshi Kunita
- Center for Experimental Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency Medicine, Oita University, Oita, Japan
| | - Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryosuke Suzuki
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Koji Ishii
- Department of Quality Assurance and Radiological Protection, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Department of Infectious Diseases and Applied Immunology, Hospital of the Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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Zimmermann L, Chlanda P. Cryo-electron tomography of viral infection - from applications to biosafety. Curr Opin Virol 2023; 61:101338. [PMID: 37348443 DOI: 10.1016/j.coviro.2023.101338] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 04/25/2023] [Accepted: 05/28/2023] [Indexed: 06/24/2023]
Abstract
Cellular cryo-electron tomography (cryo-ET) offers 3D snapshots at molecular resolution capturing pivotal steps during viral infection. However, tomogram quality depends on the vitrification level of the sample and its thickness. In addition, mandatory inactivation protocols to assure biosafety when handling highly pathogenic viruses during cryo-ET can compromise sample preservation. Here, we focus on different strategies applied in cryo-ET and discuss their advantages and limitations with reference to severe acute respiratory syndrome coronavirus 2 studies. We highlight the importance of virus-like particle (VLP) and replicon systems to study virus assembly and replication in a cellular context without inactivation protocols. We discuss the application of chemical fixation and different irradiation methods in cryo-ET sample preparation and acquisition workflows.
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Affiliation(s)
- Liv Zimmermann
- Schaller Research Groups, Department of Infectious Diseases, Virology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Petr Chlanda
- Schaller Research Groups, Department of Infectious Diseases, Virology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
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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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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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