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Mbencho MN, Hafza N, Cao LC, Mingo VN, Nyarko-Afriyie E, Achidi EA, Ghogomu SM, Velavan TP. Prevalence, genotype distribution, and risk factors of Hepatitis E virus in blood donors, HIV patients, and pregnant women in Southwest Cameroon. Diagn Microbiol Infect Dis 2025; 111:116748. [PMID: 39961224 DOI: 10.1016/j.diagmicrobio.2025.116748] [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: 12/31/2024] [Revised: 02/06/2025] [Accepted: 02/13/2025] [Indexed: 03/03/2025]
Abstract
Most HEV infections are self-limiting, but pregnant women in their third trimester and immunocompromised individuals, such as those with HIV, face risks, including fatal liver failure and chronic infection. This study investigates HEV prevalence and genotypes in healthy blood donors and high-risk groups, such as HIV patients and pregnant women, in Southwest Cameroon, where surveillance is limited. A cross-sectional study conducted between March and June 2023 recruited 712 participants: 289 blood donors, 233 HIV patients, and 190 pregnant women. Serum and stool samples were tested for anti-HEV IgG and IgM antibodies using ELISA, and HEV RNA was detected by nested PCR targeting the ORF1 and ORF2 regions. HEV RNA-positive samples were sequenced, and genotypes identified. Among the 712 participants, 7 % tested positive for anti-HEV IgG and 2 % for anti-HEV IgM. Blood donors had the highest anti-HEV IgG prevalence (9 %). No significant associations were found between HEV seropositivity and demographic or dietary risk factors. The overall HEV RNA positivity rate was 1 %, with the highest rates in blood donors (2 %) and pregnant women (1 %), while no cases were found in HIV patients. Phylogenetic analysis revealed that 75 % of HEV RNA-positive samples belonged to genotype 3a, and 25 % to genotype 3e. The nucleotide diversity between human and pig HEV genotype 3 suggests the involvement of environmental or other indirect transmission routes, rather than direct pig-to-human transmission. This study highlights HEV risk in Cameroon, especially among blood donors and pregnant women, underscoring the need for enhanced surveillance in HBV-endemic regions.
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Affiliation(s)
- Macqueen Ngum Mbencho
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Molecular and Cell Biology Laboratory, University of Buea, Buea, Cameroon
| | - Nourhane Hafza
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Le Chi Cao
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Department of Parasitology, Hue University of Medicine and Pharmacy (HUMP), Hue University, Hue, Vietnam
| | - Victorine Ndiwago Mingo
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Molecular and Cell Biology Laboratory, University of Buea, Buea, Cameroon
| | - Emmanuella Nyarko-Afriyie
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana
| | - Eric A Achidi
- Faculty of Sciences, University of Buea, Buea, Cameroon
| | - Stephen Mbigha Ghogomu
- Molecular and Cell Biology Laboratory, University of Buea, Buea, Cameroon.; Faculty of Sciences, University of Buea, Buea, Cameroon
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese German Center for Medical Research (VG-CARE), Hanoi, Vietnam; Faculty of Medicine, Duy Tan University, Da Nang, Vietnam.
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Haase JA, Schlienkamp S, Ring JJ, Steinmann E. Transmission patterns of hepatitis E virus. Curr Opin Virol 2025; 70:101451. [PMID: 39892085 DOI: 10.1016/j.coviro.2025.101451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/03/2025]
Abstract
Hepatitis E virus (HEV) causes sporadic cases in industrialized countries and endemic outbreaks in areas with lower sanitation standards. The wide host reservoir of HEV makes it a potential source of new zoonotic transmission and dissemination in humans. Thus, the perception of HEV as a confined ailment has shifted to one of global concern. Considering HEV's environmental stability and heterogeneity in the host range of HEV's genotypes, various transmission pathways and sources for HEV infections are plausible. Here, we provide an overview on HEV's transmission routes and discuss the role of HEV as a foodborne zoonosis, as well as preventive measures and open research questions.
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Affiliation(s)
- Jil A Haase
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Sarah Schlienkamp
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Julian J Ring
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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Singson S, Shastry S, Sudheesh N, Chawla K, Madiyal M, Kandasamy D, Mukhopadhyay C. Assessment of Hepatitis E virus transmission risks: a comprehensive review of cases among blood transfusion recipients and blood donors. Infect Ecol Epidemiol 2024; 14:2406834. [PMID: 39421644 PMCID: PMC11486055 DOI: 10.1080/20008686.2024.2406834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 09/17/2024] [Indexed: 10/19/2024] Open
Abstract
Background Hepatitis E Virus is a major cause of acute and fulminant hepatitis, particularly in developing countries. While the virus is commonly spread through the fecal-oral route, numerous cases of transfusion transmitted Hepatitis E Virus (TT-HEV) have been reported, raising concerns about its transmission via blood transfusions, especially in industrialized countries. The high prevalence of antibodies and viremia among asymptomatic blood donors further heightens the risk of transfusion-related transmission. However, there is still debate about the best strategy to minimize TT-HEV. Objective The review was conducted to Summarize the literature on TT-HEV infection cases and the prevalence of HEV among blood donors. Methods The databases PubMed, Scopus, Web of Science, Embase, and CINAHL were searched for relevant studies from 2000 to 2022.Serological and molecular screening data of HEV in blood donors were used to gather prevalence and incidence rates.TT-HEV cases were reviewed by examining evidence of HEV infection before and after transfusion. Results A total of 121 manuscripts reports the prevalence and incidence of HEV among blood donors and cases of TT-HEV. Twenty-six articles reported confirmed cases of TT-HEV and 101 articles reported on HEV prevalence or incidence among blood donors. Conclusion TT-HEV transmission through blood products is a real concern, especially for immunocompromised patients.The risk and severity of infection could vary between immunocompetent and immunosuppressed patients.To increase transfusion safety, the evaluation recommends HEV screening protocols, especially in endemic region.
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Affiliation(s)
- Sangthang Singson
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Shamee Shastry
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - N. Sudheesh
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Kiran Chawla
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Mridula Madiyal
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Dhivya Kandasamy
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnatka, India
| | - Chiranjay Mukhopadhyay
- Department of Microbiology, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, Karnataka, India
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
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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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Nagoba BS, Rayate AS. Hepatitis E virus infections. World J Virol 2024; 13:90951. [PMID: 38984082 PMCID: PMC11229837 DOI: 10.5501/wjv.v13.i2.90951] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/02/2024] [Accepted: 04/07/2024] [Indexed: 06/24/2024] Open
Abstract
Hepatitis E virus (HEV) infection is now endemic worldwide. Most patients with acute infection recover uneventfully. Outbreaks and sporadic cases, particularly in high-risk individuals are emerging increasingly. The patients with risk factors like pregnancy and pre-existing chronic liver disease, present with or progress rapidly to severe disease. Immuno-suppression in post-transplant patients is an additional risk factor. Standardized FDA-approved diagnostic tests are the need of the hour. Further studies are needed to establish guideline-based treatment regimen and outbreak preparedness for HEV to decrease global morbidity, mortality, and healthcare burden. Policies for screening donors and transplant cases are required.
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Affiliation(s)
- Basavraj S Nagoba
- Department of Microbiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, India
| | - Abhijit S Rayate
- Department of Surgery, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, India
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Copado-Villagrana ED, Pizuorno A, García-Suárez A, Abarca JC, DuPont G, Jaramillo-Bueno S, Fierro NA. IL-18 discriminates highly frequent hepatitis E virus positive from negative blood donors in Mexico. Ann Hepatol 2023; 28:101117. [PMID: 37268060 DOI: 10.1016/j.aohep.2023.101117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 06/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis E virus (HEV) is not routinely screened in blood banks in low- and middle-income countries, and no specific biomarkers of exposure to this virus have yet been identified. We aimed to identify HEV seropositivity and detect virus RNA among blood donors from Mexico to further correlate risk factors related to infection and levels of interleukin-18 (IL-18) and interferon-gamma (IFN-γ) as potential biomarkers. MATERIALS AND METHODS This cross-sectional, single-center study included 691 serum samples of blood donors obtained in 2019. Anti-HEV IgG and IgM antibodies were detected in sera and the viral genome was screened in pooled samples. A statistical comparison of risk factors for infection, demographic and clinical features was performed; IL-18 and IFN- γ values were tested in sera. RESULTS Of all the individuals, 9.4% were positive for anti-HEV antibodies and viral RNA detection was confirmed in one of the pools positive for anti-HEV. From the analysis of risk factors, age and having pets were statistically significant for anti-HEV antibody detection. Seropositive samples showed significantly higher IL-18 concentrations relative to samples from seronegative donors. Interestingly, IL-18 values were similar when HEV seropositive samples were compared to samples from clinically acute previously confirmed HEV patients. CONCLUSIONS Our findings highlight the need to follow up on HEV in blood banks in Mexico and underscore that IL-18 could represent a biomarker of HEV exposure.
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Affiliation(s)
| | - Antonio Pizuorno
- Department of Internal Medicine, Health Science Center, The University of Texas, Houston 77030, USA
| | - Adrián García-Suárez
- Department of Immunology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - Julio C Abarca
- Department of Immunology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - Gisela DuPont
- Department of Immunology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - Socorro Jaramillo-Bueno
- Regional General Hospital Number 45, Mexican Social Security Institute, Guadalajara 44100, Mexico
| | - Nora A Fierro
- Department of Immunology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City 04510, Mexico.
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Franz A, Reuken PA, Guliyeva S, Rose M, Boden K, Stallmach A, Bruns T. Early ribavirin for hepatitis E virus infection in patients receiving immunosuppressive therapy: a retrospective, observational study. J Int Med Res 2023; 51:3000605231187941. [PMID: 37523153 PMCID: PMC10392516 DOI: 10.1177/03000605231187941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023] Open
Abstract
OBJECTIVE Hepatitis E virus (HEV) infections are common, self-limiting causes of acute viral hepatitis. This study aimed to analyze hepatic injury, viremia, and chronicity rates in patients with acute HEV infection receiving immunosuppressive (IS) therapy taking into account ribavirin treatment. METHODS In this retrospective, single-center, observational study, we analyzed the disease course of 25 non-cirrhotic patients receiving IS therapy who were diagnosed with acute HEV viremia. Forty-four patients with acute HEV viremia without IS therapy were controls. RESULTS Demographics, symptoms at presentation, and extrahepatic manifestations were not different between patients with and without IS therapy, but liver injury at presentation was less severe in patients with IS therapy. Among the patients with IS therapy, 18 (72%) received ribavirin for a median of 56 days. Sustained viral clearance was observed in 21 patients with IS therapy, whereas 3 patients relapsed after ribavirin, and 1 patient had viral persistence. Among patients with sustained viral clearance, there was a longer duration of viremia in patients with IS therapy than in those without. CONCLUSIONS In this cohort of non-cirrhotic patient with IS, early treatment with ribavirin for acute HEV infection did not improve viral clearance rates, but may have shortened the duration of viremia.
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Affiliation(s)
- Anika Franz
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Philipp A Reuken
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Sura Guliyeva
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Rose
- Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
| | - Katharina Boden
- Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
- Dianovis GmbH, Greiz, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Hanno AEF, Khouly EE, Abdel-Rauof M, Moghazy A, Dauod S. Seroprevalence of hepatitis E viral infection among apparently healthy personnels and patients with certain neurological disorders in Alexandria University Hospitals. EGYPTIAN LIVER JOURNAL 2023; 13:30. [DOI: 10.1186/s43066-023-00266-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 06/14/2023] [Indexed: 09/02/2023] Open
Abstract
Abstract
Introduction
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. There are thought to be 20 million infections per year in poorer nations with inadequate sanitation. In Egypt, awareness about the possible hazards linked to HEV infection is limited due to low socioeconomic and educational levels. Only a small number of sequences have been characterized, making HEV study in Egypt constrained. Numerous factors may have contributed to this neglect. Various extra-hepatic symptoms of HEV infection include neurological problems are recognized. Many European nations have implemented regular HEV monitoring, or targeted screening of blood provided by patients at greater risk to stop the spread of HEV by transfusion.
Aim
Assess the prevalence of HEV infection in asymptomatic blood donors. Increasing awareness about HEV testing in patients with some unexplained neurological disorders.
Methods
Cross-sectional study involving 550 patients: 500 apparently healthy blood donors and 50 patients with some neurological disorders. All subjects were tested for serological markers (IgG and IgM) for HEV using ELISA technique in addition to HEV RNA PCR testing for seropositive patients.
Results
Five hundred asymptomatic blood donors (370 males and 130 females), ages ranging from 20 to 50 years (median 33), 22.6% of them tested positive for HEV (IgG and IgM) of which 2 subjects only had positive HEV RNA PCR testing. In the second group 50 patients (26 males and 24 females) with various unexplained neurological disorders. Liver functions were within normal or showed only a mild increase. Forty-four percent of the patients had positive serology for HEV, with 6 patients testing positive for HEV RNA on PCR.
Conclusion
No need for mass screening for HEV serology among blood donors. HEV infection needs to be considered in patients with unexplained neurological disorders even if the liver functions are not markedly elevated.
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Li M, Lv Y, Cui D, Xu Y, Lin M, Zhang X, Wang Y, Shen C, Xie J. Development and clinical validation of a one-step pentaplex real-time reverse transcription PCR assay for detection of hepatitis virus B, C, E, Treponema pallidum, and a human housekeeping gene. BMC Infect Dis 2023; 23:358. [PMID: 37231355 DOI: 10.1186/s12879-023-08240-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 04/11/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND With the safety of blood transfusion being a major public health concern, the development of a rapid, sensitive, specific, and cost-effective multiplex PCR assay for simultaneous detection of hepatitis B virus(HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and Treponema pallidum(T. pallidum) in blood is crucial. METHODS Five primer pairs and probes were designed towards conserved regions of target genes and used to establish a one-step pentaplex real-time reverse transcription PCR(qRT-PCR) assay for simultaneous detection of HBV, HCV, HEV, T. pallidum, and RNase P(housekeeping gene), providing sample quality check. The clinical performance of the assay was further determined with 2400 blood samples from blood donors and patients in Zhejiang province, and compared the results with commercial singleplex qPCR and serological assays. RESULTS The 95% limit of detection(LOD) of HBV, HCV, HEV, and T. pallidum were 7.11 copies/µL, 7.65 copies/µL, 8.45 copies/µL, and 9.06 copies/µL, respectively. Moreover, the assay has good specificity and precision. Compared to the singleplex qPCR assay, the novel assay for detecting HBV, HCV, HEV, and T. pallidum presented 100% clinical sensitivity, specificity, and consistency. Several discrepant results between serological and pentaplex qRT-PCR assays were found. Of 2400 blood samples, there were 2(0.08%) HBsAg positive samples, 3(0.13%) anti-HCV positive samples, 29(1.21%) IgM anti-HEV positive samples and 6(0.25%) anti-T. pallidum positive samples proven negative in nucleic acid detection. 1(0.04%) HBV DNA positive sample and 1(0.04%) HEV RNA positive sample were detected negative by serological testing. CONCLUSIONS The developed pentaplex qRT-PCR is the first assay on simultaneous, sensitive, specific, and reproducible detection of HBV, HCV, HEV, T. pallidum, and RNase P in a single tube. It could detect pathogens in blood during the window period of infection and is a good tool for effectively screening blood donors and early clinical diagnosis.
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Affiliation(s)
- Miaomiao Li
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yan Lv
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Dawei Cui
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yushan Xu
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Mengjiao Lin
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | | | - Yongjun Wang
- Key Laboratory of Blood Safety Research of Zhejiang Province, Zhejiang Province Blood Center, Hangzhou, 310052, China
| | - Cuifen Shen
- Department of Clinical Laboratory, Huzhou Central Hospital, Huzhou, 313000, China.
| | - Jue Xie
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Mättö J, Putkuri N, Rimhanen-Finne R, Laurila P, Clancy J, Ihalainen J, Ekblom-Kullberg S. Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population. Pathogens 2023; 12:pathogens12030484. [PMID: 36986406 PMCID: PMC10054892 DOI: 10.3390/pathogens12030484] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016-2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6-7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.
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Affiliation(s)
- Jaana Mättö
- Finnish Red Cross Blood Service, 01730 Vantaa, Finland
| | - Niina Putkuri
- Finnish Red Cross Blood Service, 01730 Vantaa, Finland
| | | | - Päivi Laurila
- Finnish Institute for Health and Welfare, 00100 Helsinki, Finland
| | - Jonna Clancy
- Finnish Red Cross Blood Service Biobank, 01730 Vantaa, Finland
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Gravemann U, Engelmann M, Kinast V, Burkard T, Behrendt P, Schulze TJ, Todt D, Steinmann E. Hepatitis E virus is effectively inactivated by methylene blue plus light treatment. Transfusion 2022; 62:2200-2204. [PMID: 36125237 DOI: 10.1111/trf.17108] [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: 03/01/2022] [Revised: 08/23/2022] [Accepted: 08/23/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND OBJECTIVES Photodynamic treatment with methylene blue (MB) and visible light is a well-established pathogen inactivation system for human plasma. This technique is routinely used in different countries. MB/light treatment was shown to inactivate several transfusion-transmittable viruses, but its efficiency for the inactivation of the quasi-enveloped hepatitis E virus (HEV) has not yet been investigated. MATERIALS AND METHODS Plasma units were spiked with cell culture-derived HEV and treated with the THERAFLEX MB-Plasma system using various light doses (30, 60, 90, and 120 J/cm2 ). HEV titers in pre- and post-treatment samples were determined by virus titration and a large-volume plating assay to improve the detection limit of the virus assay. RESULTS THERAFLEX MB-Plasma efficiently inactivated HEV in human plasma. Even the lowest light dose of 30 J/cm2 inactivated HEV down to the limit of detection, with a mean log reduction factor of greater than 2.4 for the total process. CONCLUSION Our study demonstrates that the THERAFLEX MB-Plasma system effectively inactivates HEV in human plasma.
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Affiliation(s)
- Ute Gravemann
- German Red Cross Blood Service NSTOB, Springe, Germany
| | - Michael Engelmann
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Volker Kinast
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.,Department of Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Thomas Burkard
- 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, Hannover, Germany.,German Centre for Infection Research, Hannover, Germany
| | | | - Daniel Todt
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.,European Virus Bioinformatics Center (EVBC), Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.,German Centre for Infection Research (DZIF), External Partner Site, Bochum, 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: 18] [Impact Index Per Article: 6.0] [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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Aggarwal R, Goel A. Hepatitis E: Current Status in India. Clin Liver Dis (Hoboken) 2021; 18:168-172. [PMID: 34691406 PMCID: PMC8518337 DOI: 10.1002/cld.1146] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/30/2021] [Accepted: 06/04/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Rakesh Aggarwal
- Jawaharlal Institute of Postgraduate Medical Education and ResearchPuducherryIndia
| | - Amit Goel
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
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Dichtl K, Zimmermann J, Koeppel MB, Böhm S, Osterman A. Evaluation of a Novel CLIA Monotest Assay for the Detection of Anti-Hepatitis E Virus-IgG and IgM: A Retrospective Comparison with a Line Blot and an ELISA. Pathogens 2021; 10:pathogens10060689. [PMID: 34206114 PMCID: PMC8228023 DOI: 10.3390/pathogens10060689] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/27/2022] Open
Abstract
Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; recomLine HEV, Mikrogen) and an ELISA (EIA; Anti-Hepatitis E Virus ELISA, Euroimmun) with a novel chemoluminescence immunoassay in a monotest format (CLIA; Hepatitis E VirClia, Vircell). Twenty sera of PCR proven cases of hepatitis E and 68 blood samples serologically pre-characterized were included. Applying the WHO reference standard, the CLIA demonstrated the highest analytical sensitivity for IgG and IgM. The combinations of CLIA/EIA (IgG and IgM) and CLIA/LIA (IgG) measurements showed substantial correlation. Compared to overall antibody detection (seropositivity in ≥2 assays), CLIA correlation was excellent, outperforming LIA (IgM) and EIA (IgG and IgM). Minor IgM cross reactivity in samples of patients with acute EBV infection was observed in all three assays. The CLIA showed good performance in diagnostic samples compared to established LIA and EIA assays. Due to its ready-to-use monotest format, the CLIA allows simple, time- and cost-effective handling of single samples. These qualities make the assay suitable for diagnostics, especially in the emergency setting and for low-throughput laboratories.
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Affiliation(s)
- Karl Dichtl
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
| | - Julia Zimmermann
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | | | - Stephan Böhm
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | - Andreas Osterman
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
- Correspondence:
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15
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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: 6] [Impact Index Per Article: 1.5] [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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Mishra KK, Patel K, Trivedi A, Patel P, Ghosh K, Bharadva S. Risk of hepatitis-E virus infections among blood donors in a regional blood transfusion centre in western India. Transfus Med 2021; 31:193-199. [PMID: 33738857 DOI: 10.1111/tme.12760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/02/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hepatitis-E virus (HEV) is an emerging infectious threat to blood safety. The enormity of the transmission of HEV and its clinical consequence are issues currently under debate. This study aimed to evaluate the prevalence of HEV-RNA in blood donors in western India. MATERIALS AND METHODS We screened 13 050 blood donors for HEV using HEV-RNA screening of 10 mini-pools using RealStar HEV RT-PCR Kit (95% limit of detection (LOD): 4.7 IU/ml). Furthermore, all HEV-RNA-positive donors were investigated for the presence of IgM/IgG antibody along with liver function tests. RESULTS Of the 13 050 blood donations, 7 (0.53%) were found to be HEV-RNA positive, and the prevalence of HEV nucleic acid testing yield cases among blood donors was 1 in 1864. All seven HEV-RNA-positive samples were tested with anti-HEV IgM and anti-HEV IgG antibodies; this resulted in two (28.5%) positive anti-HEV IgM and two (28.5%) positive anti-HEV IgG antibodies. Hepatic activity was measured, with two of seven HEV-RNA-positive donors demonstrating abnormal serum glutamic oxaloacetic transaminase (SGOT) andserum glutamic pyruvic transaminase (SGPT). Two HEV-RNA-positive blood donors who had abnormal SGOT and SGPT were found to have a high HEV viral load. Furthermore, we were able to follow up two HEV-RNA donors, and both were HEV-RNA positive and had anti-HEV IgM and anti-HEV IgG antibodies; moreover, their liver function tests were also abnormal. One of the HEV-RNA donors with high viral load did show hepatitis-E-like virus on electron microscopy. CONCLUSION Our studies indicate that there is a significant risk of blood-borne transmission of HEV. This finding may help to provide a direction towards the safety of blood transfusions in clinical settings in countries like India, which fall under the endemic category for HEV infection.
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Affiliation(s)
- Kanchan K Mishra
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Krima Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Apeksha Trivedi
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Parizad Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Kanjaksha Ghosh
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Sumit Bharadva
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
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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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Risk of Hepatitis E among Persons Who Inject Drugs in Hong Kong: A Qualitative and Quantitative Serological Analysis. Microorganisms 2020; 8:microorganisms8050675. [PMID: 32384808 PMCID: PMC7284329 DOI: 10.3390/microorganisms8050675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/01/2020] [Accepted: 05/05/2020] [Indexed: 11/21/2022] Open
Abstract
Hepatitis E virus (HEV) is an important cause of hepatitis, which can be transmitted via the bloodborne route. However, risk of hepatitis E among persons who inject drugs (PWIDs) is poorly understood. This study aimed to elucidate whether PWIDs are at risk for hepatitis E. We performed HEV IgM, IgG and nucleic acid detection on a cohort of 91 PWIDs and 91 age- and sex-matched organ donors. Blood HEV IgG was measured using the WHO HEV antibody standard. The effects of age, gender and addictive injection use on HEV serostatus and concentration were assessed. HEV IgG seroprevalence was 42/91 (46.2%) in the PWID group and 20/91 (22%) in the donor group (odds ratio = 3.04 (1.59–5.79), p = 0.0006). The median HEV IgG concentration was 5.8 U/mL (IQR: 2.5–7.9) in the PWID group and 2.1 U/mL (IQR: 1.2–5.3) in the donor group (p = 0.005). Increasing age and addictive injection use were significantly associated with HEV IgG serostatus, but only addictive injection use was associated with HEV IgG concentration (p = 0.024). We conclude that PWIDs are at increased risk for hepatitis E and are prone to repeated HEV exposure and reinfection as indicated by higher HEV IgG concentrations.
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