|
1
|
Serricchio M, Gowland P, Widmer N, Stolz M, Niederhauser C. HEV in Blood Donors in Switzerland: The Route to Safe Blood Products. Pathogens 2024; 13:911. [PMID: 39452782 PMCID: PMC11510004 DOI: 10.3390/pathogens13100911] [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: 08/21/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
The hepatitis E virus (HEV) is an emerging infectious disease with zoonotic potential, causing acute hepatitis in humans. Infections in healthy individuals are often acute, self-limiting and asymptomatic, thus leading to the underdiagnosis of HEV infections. Asymptomatic HEV infections pose a problem for blood transfusion safety by increasing the risk for transfusion-transmitted HEV infections. Here, we describe the journey from determining the HEV seroprevalence among blood donors to the implementation of routine HEV RNA testing of all blood products in Switzerland in 2018 and summarise the HEV cases detected since. In total, 290 HEV-positive blood donations were detected by mini-pool nucleic acid testing (NAT) in Switzerland in the period of October 2018-December 2023, equal to an incidence of 20.7 per 100,000 donations. Thanks to the implemented scheme, no transfusion-transmitted infections occurred in this period. Furthermore, blood donation monitoring has proven to be an effective means of detecting HEV outbreaks in the general population. HEV cases in Swiss blood donors are caused by two major genotypes, the Swiss-endemic subtypes 3h3 and 3c. Interestingly, 11 HEV cases (5%) were of genotype 3ra, a variant found in wild and farmed rabbits. Our results indicate that mini-pool NAT is an efficient method to reduce the risk of transfusion-transmitted HEV infections.
Collapse
Affiliation(s)
- Mauro Serricchio
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Martin Stolz
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
| | - Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Bern, Switzerland; (M.S.); (P.G.); (M.S.)
- Institute for Infectious Diseases, University of Bern, 3012 Bern, Switzerland
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
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.
Collapse
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
| |
Collapse
|
|
4
|
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.
Collapse
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.)
| |
Collapse
|
|
5
|
Cardoso M, Ragan I, Hartson L, Goodrich RP. Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies. Pathogens 2023; 12:911. [PMID: 37513758 PMCID: PMC10383627 DOI: 10.3390/pathogens12070911] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/30/2023] [Accepted: 07/02/2023] [Indexed: 07/30/2023] Open
Abstract
Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human-animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions.
Collapse
Affiliation(s)
- Marcia Cardoso
- Terumo BCT, Inc., TERUMO Böood and Cell Technologies, Zaventem, 41 1930 Brussels, Belgium
| | - Izabela Ragan
- Infectious Disease Research Center, Department of Biomedical Science, Colorado State University, Fort Collins, CO 80521, USA
| | - Lindsay Hartson
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| | - Raymond P Goodrich
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| |
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens 2023; 12:pathogens12030425. [PMID: 36986347 PMCID: PMC10059948 DOI: 10.3390/pathogens12030425] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/10/2023] Open
Abstract
Background and aims: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Methods: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. Results: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Conclusions: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost–benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
Collapse
|
|
8
|
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.
Collapse
|
|
9
|
Filipe R, Prista-Leão B, Silva-Pinto A, Abreu I, Serrão R, Costa R, Guedes E, Sobrinho-Simões J, Sarmento A, Koch C, Santos L. Hepatitis E in a Portuguese cohort of human immunodeficiency virus positive patients: High seroprevalence but no chronic infections. Health Sci Rep 2022; 5:e624. [PMID: 35601036 PMCID: PMC9121181 DOI: 10.1002/hsr2.624] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/31/2022] [Accepted: 03/21/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction Hepatitis E virus (HEV) infection causes zoonotic hepatitis in Europe, with a higher risk of complications in immunocompromised hosts. HEV natural history in human immunodeficiency virus (HIV) positive patients is not fully understood, and its prevalence is unknown. Objectives To study the seroprevalence of HEV and prevalence of chronic HEV in HIV‐positive patients from Porto, Portugal. Methods We randomly selected patients from the cohort of HIV‐positive patients followed in our hospital. We performed an enzyme‐linked immunosorbent assay to search for immunoglobulin G for HEV. When the absorbance/cut‐off was inferior to 3.5, the test was repeated, and a confirmatory test executed in that sample. For reactive tests and for immunosuppressed patients (CD4 count < 200/mm3) with nonreactive test, a polymerase chain reaction (PCR) test was also performed. Results We included 299 patients. The mean age was 48 and 75.3% were men. Regarding HIV infection, the median follow‐up time was 10 years, the acquisition was mainly heterosexual contact, and 94% were on antiretroviral therapy. Seventy‐six patients (25.4%) had reactive immunoglobulin G (IgG) hepatitis E serology. Patients with a reactive test were older (statistically significant difference). Otherwise, there was no difference between groups concerning birthplace, rural residence, chronic viral hepatitis coinfection, or cirrhosis. Nadir and actual TCD4+ lymphocyte counts did not differ significantly from patients with HEV reactive and nonreactive serology. Gamma‐glutamyl‐transferase (GGT) was higher in patients with reactive IgG HEV. All serum HEV PCR tests were negative. Conclusions Seroprevalence of HEV was 25.4% in HIV‐positive patients. Older age and higher GGT correlated to HEV reactive IgG test. No cases of current hepatitis E were found.
Collapse
Affiliation(s)
- Rita Filipe
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Beatriz Prista-Leão
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - André Silva-Pinto
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal.,ESCMID Study Group for Immunocompromised Hosts-ESGICH Porto Portugal
| | - Isabel Abreu
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Rosário Serrão
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal
| | - Rosário Costa
- Clinical Pathology Department Centro Hospitalar Universitário de São João Porto Portugal
| | - Edite Guedes
- Imunohemotherapy Department Centro Hospitalar Universitário São João Porto Portugal
| | - Joana Sobrinho-Simões
- Clinical Pathology Department Centro Hospitalar Universitário de São João Porto Portugal
| | - António Sarmento
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal
| | - Carmo Koch
- Imunohemotherapy Department Centro Hospitalar Universitário São João Porto Portugal
| | - Lurdes Santos
- Infectious Diseases Department Centro Hospitalar Universitário de São João Porto Portugal.,Faculty of Medicine University of Porto Porto Portugal.,ESCMID Study Group for Immunocompromised Hosts-ESGICH Porto Portugal
| |
Collapse
|
|
10
|
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.
Collapse
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
| |
Collapse
|
|
11
|
Al Dossary RA, Alnafie AN, Aljaroodi SA, Rahman JU, Hunasemarada BC, Alkharsah KR. Prevalence of Hepatitis E Virus Infection Among Blood Donors in the Eastern Province of Saudi Arabia. J Multidiscip Healthc 2021; 14:2381-2390. [PMID: 34475765 PMCID: PMC8407670 DOI: 10.2147/jmdh.s328029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/16/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Hepatitis E virus (HEV) causes acute hepatitis in humans and constitutes a major problem for immunocompromised patients, patients with hematological diseases, and pregnant women. It is transmitted mainly through fecal oral route; however, transmission through blood and blood products is reported globally and becoming a health concern. We sought to determine the prevalence of HEV among blood donors in the Eastern Province of Saudi Arabia using molecular as well as serological assays to assess the safety of blood transfusion and the need for HEV screening among blood donors. PATIENTS AND METHODS A total of 806 whole blood samples were collected from blood donors between May and November 2020 and tested for anti-HEV IgG and IgM antibodies by ELISA and for HEV RNA by RT-PCR. RESULTS The overall seroprevalence of HEV IgG antibodies was 3.2% with no statistically significant difference between the non-Saudis (3.28%) and Saudis (3.17%) (p value 0.929) or between males (3.14%) and females (4.88%) (p value 0.527). None of the IgG positive individuals had IgM antibodies. HEV RNA was not detected in any of the blood donors. CONCLUSION HEV seroprevalence is low among blood donors in the Eastern Province of Saudi Arabia and may constitute minimal risk for transfusion associated infections.
Collapse
Affiliation(s)
- Reem A Al Dossary
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Awatif N Alnafie
- Department of Pathology, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Salma Ali Aljaroodi
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Jawad Ur Rahman
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Basavaraj C Hunasemarada
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Khaled R Alkharsah
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| |
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
Seroprevalence of Hepatitis E Virus Infection among Blood Donors in Bulgaria. Viruses 2021; 13:v13030492. [PMID: 33809748 PMCID: PMC8002317 DOI: 10.3390/v13030492] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) infection is widespread among domestic pigs, industrial swine, and wild boars in Bulgaria. The aim of the current research was to present the HEV seroprevalence among blood donors in Bulgaria. In the present study, 555 blood donors (479 males and 76 females) were enrolled from five districts in the country (Shumen, Pleven, Stara Zagora, Plovdiv, and Sofia districts). All blood samples were tested for anti-HEV IgG using the recomWell HEV IgG ELISA test (Mikrogen GmbH, Neuried, Germany). Each participating donor completed a short, structured, and specific questionnaire to document data on the current study. Anti-HEV IgG positive results were detected in 144 (25.9%) blood donors, including 129 (26.9%) males and 15 (19.7%) females. The established HEV seropositivity was 28.8% (23/80) in Shumen district, 23.2% (22/95) in Pleven district, 27.1% (38/140) in Stara Zagora district, 27.5% (44/160) in Plovdiv district, and 21.3% (17/80) in Sofia district. A high HEV seroprevalence was found for persons who declared that they were general hunters (48.7%; 19/39; p = 0.001) and hunters of wild boars (51.6%; 16/31; p = 0.001). We present the first seroprevalence rates of HEV infection in blood donors from Bulgaria. The results of our research showed high HEV seropositivity among blood donors.
Collapse
|
|
14
|
Capai L, Hozé N, Chiaroni J, Gross S, Djoudi R, Charrel R, Izopet J, Bosseur F, Priet S, Cauchemez S, de Lamballerie X, Falchi A, Gallian P. Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017. ACTA ACUST UNITED AC 2020; 25. [PMID: 32046820 PMCID: PMC7014670 DOI: 10.2807/1560-7917.es.2020.25.5.1900336] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Hepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV. Aim Our aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection. Methods Between September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay. Results The overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults). Conclusion We confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.
Collapse
Affiliation(s)
- Lisandru Capai
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Jacques Chiaroni
- Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| | - Sylvie Gross
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rachid Djoudi
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rémi Charrel
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Jacques Izopet
- Institut National de la Santé et de la Recherche Médicale Unité 1043, Université Toulouse III, Toulouse, France.,Laboratoire de Virologie, Institut Fédératif de Biologie, Centre Hospitalier et Universitaire, Toulouse, France
| | - Frédéric Bosseur
- Sciences Pour l'Environnement - UMR CNRS 6134 Université de Corse, Corte, France
| | - Stéphane Priet
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Simon Cauchemez
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Xavier de Lamballerie
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Alessandra Falchi
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Pierre Gallian
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.,Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France.,Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| |
Collapse
|
|
15
|
Perisetti A, Laoveeravat P, Inamdar S, Tharian B, Thandassery R, Goyal H. Hepatitis E virus infection in liver transplant recipients: a descriptive literature review. Eur J Gastroenterol Hepatol 2020; 32:916-922. [PMID: 32091436 DOI: 10.1097/meg.0000000000001682] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus infection has been recognized as a rising hepatotropic viral infection in the developing countries but overlooked in the developed countries, due to its lower prevalence. However, hepatitis E virus prevalence is on rise in the liver transplant recipients due to immunosuppression, which needs prompt recognition by healthcare practitioners. Hepatitis E virus infection is commonly believed to be transmitted via an animal host; but in the post-liver transplant patients, it can also be acquired via blood and blood products transfusion and autochthonous route. Previous studies have shown the significance of hepatitis E virus infection in post-liver transplant, as the patients at a high risk of progressing to chronic hepatitis and cirrhosis. Pediatric patients are at higher risk of hepatitis E virus infection post-liver transplant. Specific hepatitis E virus genotypes have the potential for greater severity. The clinical manifestation of hepatitis E virus can also present as extrahepatic features which need high level of suspicion for early recognition and treatment. Treatment options of hepatitis E virus range from immunosuppressive drug minimization, ribavirin therapy to novel direct-acting antiviral regimens. Herein, we aim to explore epidemiology, prevalence, risk factor, diagnosis, and management of hepatitis E virus infection giving special attention to liver transplant recipients.
Collapse
Affiliation(s)
- Abhilash Perisetti
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Passisd Laoveeravat
- Department of Internal Medicine, Texas Tech University Health Sciences, Lubbock, Texas
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Lubbock, Texas
| | - Benjamin Tharian
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Lubbock, Texas
| | - Ragesh Thandassery
- Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Hemant Goyal
- The Wright Center for Graduate Medical Education, Scranton, Pennsylvania
| |
Collapse
|
|
16
|
Abstract
While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.
Collapse
|
|
17
|
Wallace SJ, Swann R, Donnelly M, Kemp L, Guaci J, Murray A, Spoor J, Lin N, Miller M, Dalton HR, Hussaini SH, Gunson R, Simpson K, Stanley A, Fraser A. Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study. Aliment Pharmacol Ther 2020; 51:974-986. [PMID: 32285976 DOI: 10.1111/apt.15704] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 11/19/2019] [Accepted: 03/09/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states. AIMS To record the morbidity and mortality of HEV in Scotland. METHODS Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018. RESULTS Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre-existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV-related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40-782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85-594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01-1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02-0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty-five (6.7%) patients developed acute or acute-on-chronic liver failure with two requiring transplant. Thirty-seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain-Barré and 2 encephalitis. Forty-four (8.6%) patients developed acute kidney injury. CONCLUSION In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.
Collapse
Affiliation(s)
| | - Rachael Swann
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Mhairi Donnelly
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Linda Kemp
- Department of Gastroenterology, Ninewells Hospital, Dundee, UK
| | - Julia Guaci
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Aimee Murray
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Johannes Spoor
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Nan Lin
- Department of Mathematics, Physics and Electrical Engineering, Northumbria University, Newcastle, UK
| | - Michael Miller
- Department of Gastroenterology, Ninewells Hospital, Dundee, UK
| | - Harry R Dalton
- Department of Gastroenterology, Royal Cornwall Hospital Trust, Truro, Cornwall, UK
| | - S Hyder Hussaini
- Department of Gastroenterology, Royal Cornwall Hospital Trust, Truro, Cornwall, UK
| | - Rory Gunson
- Department of Virology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Kenneth Simpson
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Adrian Stanley
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Andrew Fraser
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| |
Collapse
|
|
18
|
Goel A, Vijay HJ, Katiyar H, Aggarwal R. Prevalence of hepatitis E viraemia among blood donors: a systematic review. Vox Sang 2020; 115:120-132. [PMID: 32030767 DOI: 10.1111/vox.12887] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 12/18/2019] [Accepted: 12/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is usually transmitted by faecal-oral route. Recent reports have documented HEV viraemia in donated blood units and HEV transmission through blood transfusion. This systematic review summarizes the available data on prevalence of HEV viraemia in blood donors. METHODS Electronic databases were searched on 17 December 2018 to identify full-text English papers reporting original data on prevalence of HEV RNA in donated blood units. Two authors independently extracted the relevant data, which were pooled using simple aggregation as well as a random-effects meta-analysis; heterogeneity was assessed using the I2 method. RESULTS In all, 59 data sets from 28 countries were identified. The available data showed marked heterogeneity. Of a total of 2 127 832 units studied, 561 (263·6 [95% confidence intervals = 242·7-286·4] per million units) tested positive for HEV RNA. On random-effects meta-analysis, the pooled prevalence was 60·9 [6·7-155·4] per million units. In the viraemic units, HEV RNA titre varied by nearly one million-fold, and most had genotype 3 HEV. The prevalence was higher in blood units with anti-HEV antibodies or elevated alanine aminotransferase. Only nearly one-fourth of viraemic units had anti-HEV antibodies. CONCLUSIONS The prevalence of HEV viraemia among healthy blood donors is low, though the available data had limited geographical representation and marked heterogeneity. There is a need for further data on HEV viraemia in blood donors from areas with non-3 HEV genotype preponderance.
Collapse
Affiliation(s)
- Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | - Harshita Katiyar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| |
Collapse
|
|
19
|
Ankcorn MJ, Tedder RS, Cairns J, Sandmann FG. Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2020; 23:309-318. [PMID: 32197726 DOI: 10.1016/j.jval.2019.09.2751] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 08/08/2019] [Accepted: 09/27/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.
Collapse
Affiliation(s)
- Michael J Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, Colindale, London, England, UK; Transfusion Microbiology, National Health Service Blood and Transplant, London, England, UK.
| | - Richard S Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, Colindale, London, England, UK; Transfusion Microbiology, National Health Service Blood and Transplant, London, England, UK; Department of Medicine, Imperial College London, London, England, UK
| | - John Cairns
- London School of Hygiene and Tropical Medicine, London, England, UK
| | - Frank G Sandmann
- London School of Hygiene and Tropical Medicine, London, England, UK; Statistics, Modelling and Economics Department, National Infection Service, Public Health England, Colindale, London, England, UK
| |
Collapse
|
|
20
|
Detection of hepatitis E virus (rabbit genotype) in farmed rabbits entering the food chain. Int J Food Microbiol 2020; 319:108507. [PMID: 31981930 DOI: 10.1016/j.ijfoodmicro.2020.108507] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/09/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis E virus (HEV) infects humans and many animal species. The rabbit HEV has been found in farmed, wild and pet rabbits as well as in human patients suggesting zoonotic transmission. Although the routes of human infection with rabbit strains are unclear a foodborne transmission is suggested especially when asymptomatically infected animals could enter the food chain. The aims of the study were an evaluation of the prevalence of HEV infections in slaughtered rabbits, identification of the virus genotype(s) and assessment of their genetic relatedness to other zoonotic HEV strains. A pair of blood and liver samples (n = 482) were collected from meat rabbits of different breeds slaughtered at the age of 2.8 to 6 months. The animals originated from 20 small-scale and 4 large-scale commercial farms operating in Poland. The presence of anti-HEV antibodies in animals was detected by the use of a recomWell HEV IgG (human) ELISA kit (Mikrogen Diagnostik) adapted to rabbit sera. The isolation of HEV and sample process control virus (feline calicivirus) RNA from homogenates of liver destined for food and virus-positive sera was performed using a QIAamp® Viral RNA Mini Kit (Qiagen). A one-step real-time reverse transcription PCR method containing a target-specific internal amplification control was used for detection of HEV. The (sub)genotype of detected rabbit HEV strains was identified based on sequence analysis of the ORF2 and ORF2/3 virus genome fragments. Anti-HEV antibodies were detected in 29 (6%) out of 482 rabbit sera samples collected from animals raised only on the small-scale rabbit farms. Four sera were also positive for HEV RNA. Viral RNA was detected in 72 (14.9%) animal livers. Analysing ELISA and PCR results using Student's t-test, there were significant differences observed in the frequency of HEV infections between rabbits from small-scale and commercial farms (t = 2.675, p = 0.015 < 0.05 for ELISA and t = 2.705, p = 0.014 < 0.05 for PCR). All detected virus strains were identified as HEV gt3 ra subtype. The results of this study provide data on the occurrence of HEV infections in rabbits entering the food chain, suggesting that a risk of foodborne HEV infection due to consumption of contaminated meat and liver exists. In this light, the presence of rabbit HEV in food animals is pertinent as an issue of food safety and the surveillance of these animals for emerging or re-emerging viruses.
Collapse
|
|
21
|
Human Immunodeficiency Virus Infected Patients are Not at Higher Risk for Hepatitis E Virus Infection: A Systematic Review and Meta-Analysis. Microorganisms 2019; 7:microorganisms7120618. [PMID: 31779204 PMCID: PMC6955890 DOI: 10.3390/microorganisms7120618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/18/2019] [Accepted: 11/21/2019] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E virus (HEV) infection is the most common cause of acute hepatitis in the world. It is not well established whether people infected with the human immunodeficiency virus (HIV) are more susceptible to infection with HEV than people not infected with HIV. Many studies have evaluated this relationship, although none are conclusive. The aim of this systematic review and meta-analysis was to assess whether patients with HIV infection constitute a risk group for HEV infection. A systematic review and meta-analysis was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), to find publications comparing HEV seroprevalences among HIV infected and uninfected populations. The analysis was matched by sex, age and geographical area, and compared patients who live with HIV and HIV-negative individuals. The odds ratio (OR) for patients with HIV was 0.87 (95% CI: 0.74-1.03) in the fixed effects meta-analysis and 0.88 (95% CI: 0.70-1.11) in random effects, with I2 = 47%. This study did not show that HIV infection was a risk factor for HEV infection when compared with those who are HIV-negative.
Collapse
|
|
22
|
Hepatitis E virus infections in Europe. J Clin Virol 2019; 120:20-26. [PMID: 31536936 DOI: 10.1016/j.jcv.2019.09.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/06/2019] [Indexed: 12/11/2022]
|
|
23
|
Niederhauser C, Widmer N, Hotz M, Tinguely C, Fontana S, Allemann G, Borri M, Infanti L, Sarraj A, Sigle J, Stalder M, Thierbach J, Waldvogel S, Wiengand T, Züger M, Gowland P. Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016. ACTA ACUST UNITED AC 2019; 23. [PMID: 30180927 PMCID: PMC6124188 DOI: 10.2807/1560-7917.es.2018.23.35.1700616] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1–21.8) of the 3,609 blood samples collected in 2014–16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8–33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.
Collapse
Affiliation(s)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, Berne Switzerland
| | | | | | - Stefano Fontana
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland.,Interregional Blood Transfusion SRC, Berne Switzerland
| | | | - Mauro Borri
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland
| | - Laura Infanti
- Blood Transfusion Service Beider Basel, Basel, Switzerland
| | - Amira Sarraj
- Blood Transfusion Service SRC Neuchâtel/Jura, Neuchâtel, Switzerland
| | - Jörg Sigle
- Blood Transfusion Service SRC, Aargau/Solothurn, Switzerland
| | | | - Jutta Thierbach
- Blood Transfusion Service SRC Nordostschweiz, St. Gallen, Switzerland
| | | | - Tina Wiengand
- Blood Transfusion Service SRC Zentralschweiz, Luzern, Switzerland
| | - Max Züger
- Blood Transfusion Service SRC Thurgau, Münsterlingen, Switzerland
| | - Peter Gowland
- Interregional Blood Transfusion SRC, Berne Switzerland
| |
Collapse
|
|
24
|
Vercouter AS, Van Houtte F, Verhoye L, González Fraile I, Blanco L, Compernolle V, Meuleman P. Hepatitis E virus prevalence in Flemish blood donors. J Viral Hepat 2019; 26:1218-1223. [PMID: 31194897 DOI: 10.1111/jvh.13161] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/29/2019] [Accepted: 05/06/2019] [Indexed: 01/18/2023]
Abstract
Transmission of hepatitis E virus (HEV) through transfusion of blood components has already been reported in several European countries. Here, we assessed the HEV prevalence in Flemish blood donors. This study is of importance in order to assess the risk of HEV transmission through blood transfusion. We analysed 38 137 blood donation samples that were collected by the Red Cross Flanders during the period May-June 2015. All samples were screened for the presence of HEV RNA and a selection for HEV-specific IgM/IgG. After pooling per 6, 11 pools reacted positive during RNA screening. Reactive pools were deconstructed, and individual samples were retested. After deconstruction, seven samples were confirmed as HEV RNA positive. Serological screening of the confirmed RNA-positive samples showed that six out of these seven samples were HEV IgM positive, of which three donors were also IgG positive. Serological screening was also performed on the samples that constituted the four initially HEV RNA reactive pools where RNA positivity was not confirmed on the individual level. In three pools, we found indirect evidence of recent HEV exposure. Within 356 randomly selected samples, 31 donations were HEV IgG positive. Here we show that at least 1:5448 of blood donations in Flanders may originate from donors that are actively infected with HEV. Upon transfusion, these donations may pose a major threat towards patients at risk. Finally, a serological analysis showed that the anti-HEV IgG prevalence in Flemish blood donors is 8.71%.
Collapse
Affiliation(s)
- Ann-Sofie Vercouter
- Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Freya Van Houtte
- Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Lieven Verhoye
- Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | | | - Lydia Blanco
- Centro de Hemoterapia y Hemodonación, Valladolid, Spain
| | - Veerle Compernolle
- Blood Service of the Belgian Red Cross-Flanders, Ghent, Belgium.,Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Philip Meuleman
- Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
25
|
Thom K, Gilhooly P, McGowan K, Malloy K, Jarvis LM, Crossan C, Scobie L, Blatchford O, Smith-Palmer A, Donnelly MC, Davidson JS, Johannessen I, Simpson KJ, Dalton HR, Petrik J. Hepatitis E virus (HEV) in Scotland: evidence of recent increase in viral circulation in humans. ACTA ACUST UNITED AC 2019; 23. [PMID: 29589577 PMCID: PMC6205259 DOI: 10.2807/1560-7917.es.2018.23.12.17-00174] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BackgroundPrevious studies showed low levels of circulating hepatitis E virus (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology. Methods: Blood donor samples from five Scottish blood centres, the minipools for routine HEV screening and liver transplant recipients were tested for HEV antibodies and RNA to determine seroprevalence and viraemia. Blood donor data were compared with results from previous studies covering 2004-08. Notified laboratory-confirmed hepatitis E cases (2009-16) were extracted from national surveillance data. Viraemic samples from blood donors (2016) and chronic hepatitis E transplant patients (2014-16) were sequenced. Results: Anti-HEV IgG seroprevalence varied geographically and was highest in Edinburgh where it increased from 4.5% in 2004-08) to 9.3% in 2014-15 (p = 0.001). It was most marked in donors < 35 years. HEV RNA was found in 1:2,481 donors, compared with 1:14,520 in 2011. Notified laboratory-confirmed cases increased by a factor of 15 between 2011 and 2016, from 13 to 206. In 2011-13, 1 of 329 transplant recipients tested positive for acute HEV, compared with six cases of chronic infection during 2014-16. Of 10 sequenced viraemic donors eight and all six patients were infected with genotype 3 clade 1 virus, common in European pigs. Conclusions: The seroprevalence, number of viraemic donors and numbers of notified laboratory-confirmed cases of HEV in Scotland have all recently increased. The causes of this change are unknown, but need further investigation. Clinicians in Scotland, particularly those caring for immunocompromised patients, should have a low threshold for testing for HEV.
Collapse
Affiliation(s)
- Katrina Thom
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| | - Pamela Gilhooly
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| | - Karen McGowan
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| | - Kristen Malloy
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| | - Lisa M Jarvis
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| | - Claire Crossan
- Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Linda Scobie
- Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Oliver Blatchford
- Department of Public Health, Glasgow University, Glasgow, United Kingdom
| | - Alison Smith-Palmer
- Health Protection Scotland, National Services Scotland, Glasgow, United Kingdom
| | - Mhairi C Donnelly
- Department of Hepatology, Division of Health Sciences, Edinburgh Medical School, Edinburgh, United Kingdom
| | - Janice S Davidson
- Scottish Liver Transplantation Unit, Royal Infirmary, Edinburgh, United Kingdom
| | | | - Kenneth J Simpson
- Department of Hepatology, Division of Health Sciences, Edinburgh Medical School, Edinburgh, United Kingdom
| | - Harry R Dalton
- Royal Cornwall Hospital and European Centre for Environment and Human Health, University of Exeter Medical School, Truro, United Kingdom
| | - Juraj Petrik
- Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
| |
Collapse
|
|
26
|
von Felden J, Alric L, Pischke S, Aitken C, Schlabe S, Spengler U, Giordani MT, Schnitzler P, Bettinger D, Thimme R, Xhaard A, Binder M, Ayuk F, Lohse AW, Cornelissen JJ, de Man RA, Mallet V. The burden of hepatitis E among patients with haematological malignancies: A retrospective European cohort study. J Hepatol 2019; 71:465-472. [PMID: 31108159 DOI: 10.1016/j.jhep.2019.04.022] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/05/2019] [Accepted: 04/30/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. METHODS We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity. RESULTS The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). CONCLUSION Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution. LAY SUMMARY Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective.
Collapse
Affiliation(s)
- Johann von Felden
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Divisions of Liver Diseases and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, Toulouse, France; UMR 152, IRD Toulouse 3 University, France
| | - Sven Pischke
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Centre for Infection Research (DZIF), Hamburg site, Hamburg, Germany
| | - Celia Aitken
- Virology, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
| | - Stefan Schlabe
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Maria Teresa Giordani
- Infectious Diseases and Tropical Medicine Unit, San Bortolo Hospital, Vicenza, Italy
| | - Paul Schnitzler
- Department of Infectious Diseases, Virology, University of Heidelberg, Germany
| | - Dominik Bettinger
- Department of Medicine II, Medical Center University of Freiburg, Germany; Berta-Ottenstein-Program, Faculty of Medicine, University of Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II, Medical Center University of Freiburg, Germany
| | - Alienor Xhaard
- Service d'hématologie-greffe, Hôpital Saint-Louis, Université Paris Diderot, Paris, France
| | - Mascha Binder
- Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan J Cornelissen
- Department of Haematology, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, Netherlands
| | - Vincent Mallet
- Hepatology Service, Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, Université Paris Descartes, Paris, France; Institut National de la Santé et de la Recherche Médicale unité 1223, Institut Pasteur, Paris, France.
| |
Collapse
|
|
27
|
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]
|
|
28
|
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.
Collapse
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
| |
Collapse
|
|
29
|
Wilhelm B, Waddell L, Greig J, Young I. Systematic review and meta-analysis of the seroprevalence of hepatitis E virus in the general population across non-endemic countries. PLoS One 2019; 14:e0216826. [PMID: 31173594 PMCID: PMC6555507 DOI: 10.1371/journal.pone.0216826] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) has commonly been associated with large waterborne outbreaks of human jaundice in endemic areas but it has been increasingly recognised as a cause of sporadic human cases of jaundice in non-endemic areas, in individuals with no history of travel. Zoonotic exposure is widely hypothesized to be an important potential transmission route in these sporadic human cases. Serosurveys conducted to determine the frequency of HEV human exposure report wide ranges in prevalence across studies and locations. Our study objective was to compute meta-analysis summary estimates of human seroprevalence of HEV IgG within countries considered HEV non-endemic, where possible, and to determine whether this varied significantly across these countries, as well as investigating the role of potential HEV seroprevalence predictors such as population age structure. MATERIALS AND METHODS A broad literature search was conducted in six electronic databases. Citations were appraised, and relevant data extracted using forms designed and pre-tested a priori. Meta-analysis and meta-regression were conducted in R, with HEV IgG seroprevalence in blood donors or the general population being the outcome of interest, and country, assay, population age and sex structure, and chronological time investigated as predictors of the outcome. RESULTS From 4163 unique citations initially captured, data were extracted from 135 studies investigating HEV serology in blood donors or the general population, of 31 countries among those categorised as 'very high human development' by the United Nations. Country of sampling and assay employed were consistently significant predictors of HEV IgG seroprevalence with chronological time being a non-significant predictor in the dataset of captured studies. CONCLUSIONS While country of sampling and assay employed were significant predictors of HEV seroprevalence, comparison of HEV seroprevalence across non-endemic countries is hampered by the lack of a gold standard assay and uncertainty regarding residual bias across studies, as well as regional differences within some countries.
Collapse
Affiliation(s)
| | - Lisa Waddell
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Judy Greig
- National Microbiology Laboratory at Guelph, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - Ian Young
- School of Occupational and Public Health, Ryerson University, Toronto, Ontario, Canada
| |
Collapse
|
|
30
|
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
| |
Collapse
|
|
31
|
Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature. Viruses 2019; 11:v11010084. [PMID: 30669517 PMCID: PMC6357031 DOI: 10.3390/v11010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/11/2022] Open
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways.
Collapse
|
|
32
|
Webb GW, Dalton HR. Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis 2019; 6:2049936119837162. [PMID: 30984394 PMCID: PMC6448100 DOI: 10.1177/2049936119837162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/08/2019] [Indexed: 12/22/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.
Collapse
Affiliation(s)
- Glynn W. Webb
- University of Manchester NHS Foundation Trust, 7 Radnor Rd London NW6 6TT Manchester, UK
| | | |
Collapse
|
|
33
|
Vollmer T, Diekmann J, Knabbe C, Dreier J. Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed? Transfusion 2018; 59:612-622. [PMID: 30548866 DOI: 10.1111/trf.15058] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/16/2018] [Accepted: 10/18/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND The cost-benefit question of general screening of blood products for the hepatitis E virus (HEV) is currently being discussed. One central question is the need for individual nucleic acid amplification techniques (NAT) screening (ID-NAT) versus minipool NAT screening (MP-NAT) approaches to identify all relevant viremias in blood donors. Here, the findings of ID-NAT versus MP-NAT in pools of 96 samples were compared. STUDY DESIGN AND METHODS From November 2017 to January 2018, a total of 10,141 allogenic blood donations from 7650 individual German blood donors were screened for the presence of HEV RNA using MP-NAT (96 samples) (RealStar HEV RT-PCR Kit) compared to ID-NAT (cobas HEV assay) on the fully automated cobas 6800 platform. RESULTS Parallel screening of MP (n = 122, 96 samples/MP) using both methods detected seven reactive pools. After pool resolution, 8 HEV RNA-positive donations were identified by the in-house detection method, whereas 17 HEV RNA-positive donations were identified by ID-NAT with the cobas HEV assay. This resulted in an incidence of 1:1268 donations (0.079%) for MP-NAT screening and 1:597 donations (0.168%) for ID-NAT screening. CONCLUSIONS The detection frequency of HEV RNA was approximately 50% higher if ID-NAT was used compared to MP-NAT. However, viral loads of ID-NAT-only samples were below 25 IU/mL and will often not result in transfusion-transmitted HEV (TT-HEV) infection, taking into account the currently known infectious dose of 5.0E + 04 IU inevitably resulting in TT-HEV infection. The clinical relevance and need for identification of these low-level HEV-positive donors still require further investigation.
Collapse
Affiliation(s)
- T Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Diekmann
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - C Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - J Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| |
Collapse
|
|
34
|
Hepatitis E prevalence in French Polynesian blood donors. PLoS One 2018; 13:e0208934. [PMID: 30532225 PMCID: PMC6286134 DOI: 10.1371/journal.pone.0208934] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 11/26/2018] [Indexed: 12/13/2022] Open
Abstract
The HEV seroprevalence in mainland France is elevated (22.4%). In contrast, anti-HEV seroprevalence appears to be lower in Oceania. However, none is available for French Polynesia. We assessed the anti-HEV IgG and IgM prevalence on samples from 300 consecutive blood donors living on Tahiti and Moorea islands. Epidemiological information was collected using a specific questionnaire. Overall IgM seroprevalence was 0.6% and overall IgG seroprevalence was 7.7%. The presence of anti-HEV IgG was associated with increasing age (p = 0.01), eating chicken offal (p = 0.01) and cooked rabbit (p = 0.02). Conversely, eating fafaru—traditional Polynesian condiment—was associated with a lower rate of anti-HEV IgG (p<0.01).). All donors who surfed or practiced va’a (traditional outrigger canoë) were HEV seronegative. The Polynesian lifestyle and the particular food consumption patterns—especially the very well cooked pork—may be the key to understand the low HEV seroprevalence in French Polynesia.
Collapse
|
|
35
|
Dalton HR, Izopet J. Transmission and Epidemiology of Hepatitis E Virus Genotype 3 and 4 Infections. Cold Spring Harb Perspect Med 2018. [PMID: 29530946 DOI: 10.1101/cshperspect.a032144] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Following the introduction of robust serological and molecular tools, our understanding of the epidemiology of zoonotic hepatitis E virus (HEV) has improved considerably in recent years. Current thinking suggests that consumption of pork meat products is the key route of infection in humans, but it is certainly not the only one. Other routes of infection include environmental spread, contaminated water, and via the human blood supply. The epidemiology of HEV genotype (gt)3 and gt4 is complex, as there are several sources and routes of infection, and it is likely that these vary between and within countries and over time.
Collapse
Affiliation(s)
- Harry R Dalton
- Royal Cornwall Hospital, Truro TR1 3LJ, United Kingdom.,European Centre for Environment and Human Health, University of Exeter, Truro TR1 3LJ, United Kingdom
| | - Jacques Izopet
- Department of Virology, Hepatitis E Virus National Reference Centre, Toulouse University Hospital, 31059 Toulouse, France.,Toulouse-Purpan Centre for Pathophysiology, INSERM UMR1043/CNRS UMR 5282, CPTP, Toulouse University Paul Sabatier, 31024 Toulouse, France
| |
Collapse
|
|
36
|
Riveiro-Barciela M, Bes M, Quer J, Valcarcel D, Piriz S, Gregori J, Llorens M, Salcedo MT, Piron M, Esteban R, Buti M, Sauleda S. Thrombotic thrombocytopenic purpura relapse induced by acute hepatitis E transmitted by cryosupernatant plasma and successfully controlled with ribavirin. Transfusion 2018; 58:2501-2505. [PMID: 30284732 DOI: 10.1111/trf.14831] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 04/27/2018] [Accepted: 04/28/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) can be transmitted by transfusion of any type of blood component, but there are few data on the potential risk of transmitting this virus and the associated complications. We provide evidence that HEV can be transmitted by cryosupernatant plasma, and that HEV infection can act as a trigger for thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS A patient with a history of TTP treated with plasmapheresis 2 months previously developed jaundice and a TTP exacerbation with purpura, thrombocytopenia, schistocytes, and undetectable ADAMTS-13 activity. He was diagnosed with acute hepatitis E and treated with ribavirin. TTP remitted with remission of HEV infection. RESULTS Traceback to determine the source of the infection showed that 1 cryosupernatant plasma among the 99 different blood components used for the patient's last plasmapheresis was positive for HEV RNA, with an estimated viral load of 5000 to 10,000 IU/mL. Phylogenetic analysis proved the transfusion-transmitted route of acute hepatitis E. CONCLUSION In a patient with TTP, acute HEV infection transmitted by cryosupernatant plasma may trigger exacerbation of TTP, which can be controlled on remission of HEV infection with ribavirin.
Collapse
Affiliation(s)
- Mar Riveiro-Barciela
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Bes
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,Transfusion Safety Laboratory, Banc de Sang i Teixits, Servei Català de la Salut, Barcelona, Spain
| | - Josep Quer
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,Lab. Malalties Hepàtiques-Hepatitis Virals, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Barcelona, Spain
| | - David Valcarcel
- Department of Hematology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, PROSICS Barcelona, Barcelona, Spain
| | - Sofia Piriz
- Lab. Malalties Hepàtiques-Hepatitis Virals, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Barcelona, Spain
| | - Josep Gregori
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,Lab. Malalties Hepàtiques-Hepatitis Virals, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Barcelona, Spain
| | - Meritxell Llorens
- Lab. Malalties Hepàtiques-Hepatitis Virals, Vall d'Hebron Institut Recerca-Hospital Universitari Vall d'Hebron (VHIR-HUVH), Barcelona, Spain
| | | | - Maria Piron
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,Transfusion Safety Laboratory, Banc de Sang i Teixits, Servei Català de la Salut, Barcelona, Spain
| | - Rafael Esteban
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Silvia Sauleda
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,Transfusion Safety Laboratory, Banc de Sang i Teixits, Servei Català de la Salut, Barcelona, Spain
| |
Collapse
|
|
37
|
King NJ, Hewitt J, Perchec-Merien AM. Hiding in Plain Sight? It's Time to Investigate Other Possible Transmission Routes for Hepatitis E Virus (HEV) in Developed Countries. FOOD AND ENVIRONMENTAL VIROLOGY 2018; 10:225-252. [PMID: 29623595 DOI: 10.1007/s12560-018-9342-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Accepted: 03/29/2018] [Indexed: 06/08/2023]
Abstract
Historically in developed countries, reported hepatitis E cases were typically travellers returning from countries where hepatitis E virus (HEV) is endemic, but now there are increasing numbers of non-travel-related ("autochthonous") cases being reported. Data for HEV in New Zealand remain limited and the transmission routes unproven. We critically reviewed the scientific evidence supporting HEV transmission routes in other developed countries to inform how people in New Zealand may be exposed to this virus. A substantial body of indirect evidence shows domesticated pigs are a source of zoonotic human HEV infection, but there is an information bias towards this established reservoir. The increasing range of animals in which HEV has been detected makes it important to consider other possible animal reservoirs of HEV genotypes that can or could infect humans. Foodborne transmission of HEV from swine and deer products has been proven, and a large body of indirect evidence (e.g. food surveys, epidemiological studies and phylogenetic analyses) support pig products as vehicles of HEV infection. Scarce data from other foods suggest we are neglecting other potential sources of foodborne HEV infection. Moreover, other transmission routes are scarcely investigated in developed countries; the role of infected food handlers, person-to-person transmission via the faecal-oral route, and waterborne transmission from recreational contact or drinking untreated or inadequately treated water. People have become symptomatic after receiving transfusions of HEV-contaminated blood, but it is unclear how important this is in the overall hepatitis E disease burden. There is need for broader research efforts to support establishing risk-based controls.
Collapse
Affiliation(s)
- Nicola J King
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand
| | - Joanne Hewitt
- Institute of Environmental Science and Research, 34 Kenepuru Drive, Kenepuru, Porirua, 5022, New Zealand.
| | - Anne-Marie Perchec-Merien
- New Zealand Ministry for Primary Industries, Pastoral House, 25 The Terrace, Wellington, New Zealand
| |
Collapse
|
|
38
|
Westhölter D, Hiller J, Denzer U, Polywka S, Ayuk F, Rybczynski M, Horvatits T, Gundlach S, Blöcker J, Schulze Zur Wiesch J, Fischer N, Addo MM, Peine S, Göke B, Lohse AW, Lütgehetmann M, Pischke S. HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients. J Hepatol 2018; 69:36-42. [PMID: 29551705 DOI: 10.1016/j.jhep.2018.02.031] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 02/05/2018] [Accepted: 02/27/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe. METHODS All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire. RESULTS Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2. CONCLUSIONS Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection. LAY SUMMARY The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.
Collapse
Affiliation(s)
- Dirk Westhölter
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. MAILTO:
| | - Jens Hiller
- Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ulrike Denzer
- Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Susanne Polywka
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Meike Rybczynski
- University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas Horvatits
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Svantje Gundlach
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Johanna Blöcker
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Julian Schulze Zur Wiesch
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Nicole Fischer
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Marylyn M Addo
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Sven Peine
- Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Burkhard Göke
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| | - Sven Pischke
- I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg-Lübeck-Borstel-Riems, German Center for Infection Research (Deutsche Zentrum für Infektionsforschung), Berlin, Germany
| |
Collapse
|
|
39
|
Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018; 68:1256-1271. [PMID: 29609832 DOI: 10.1016/j.jhep.2018.03.005] [Citation(s) in RCA: 434] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 02/08/2023]
Abstract
Infection with hepatitis E virus (HEV) is a significant cause of morbidity and mortality, representing an important global health problem. Our understanding of HEV has changed completely over the past decade. Previously, HEV was thought to be limited to certain developing countries. We now know that HEV is endemic in most high-income countries and is largely a zoonotic infection. Given the paradigm shift in our understanding of zoonotic HEV and that locally acquired HEV is now the commonest cause of acute viral hepatitis in many European countries, the focus of these Clinical Practice Guidelines will be on HEV genotype 3 (and 4).
Collapse
|
|
40
|
Hepatitis E in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps? Viruses 2018; 10:v10060285. [PMID: 29799485 PMCID: PMC6024799 DOI: 10.3390/v10060285] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/16/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus transmitted by the fecal–oral route. HEV genotypes 1 and 2 infect only humans and cause mainly waterborne outbreaks. HEV genotypes 3 and 4 are widely represented in the animal kingdom, and are mainly transmitted as a zoonosis. For the past 20 years, HEV infection has been considered an imported disease in developed countries, but now there is evidence that HEV is an underrecognized pathogen in high-income countries, and that the incidence of confirmed cases has been steadily increasing over the last decade. In this review, we describe current knowledge about the molecular biology of HEV, its clinical features, its main routes of transmission, and possible therapeutic strategies in developed countries.
Collapse
|
|
41
|
A nationwide retrospective study on prevalence of hepatitis E virus infection in Italian blood donors. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2018; 16:413-421. [PMID: 29757135 DOI: 10.2450/2018.0033-18] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 04/10/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND In Europe, hepatitis E virus (HEV) infection is mainly a food-borne zoonosis, but it can also be transmitted by blood transfusion. It is usually a mild and self-limited infection. However, immunocompromised persons, who are also those more likely to undergo blood transfusions, may develop chronic hepatitis and often cirrhosis. Since this is a potential threat to blood safety, we aimed to investigate HEV prevalence in Italian blood donors. MATERIALS AND METHODS We used plasma donations collected during 2015-2016 by blood services (BS) scattered throughout the Italian regions and intended for the production of plasma-derived medicines. Plasma samples were tested for IgG and IgM anti-HEV and for HEV RNA using validated assays. Data concerning donor's age and sex, and the location of the BS were collected. RESULTS A total of 10,011 plasma samples were tested. Overall IgG and IgM prevalence rates were 8.7 and 0.4%, respectively. No sample was HEV RNA-positive. IgG prevalence was significantly higher in males and in donors aged 44 years and over. IgG prevalence differed greatly according to region. Overall regional rates over 15% were found in Abruzzo and in Sardinia, and rates of 10-15% were found in Lazio, Umbria and the Marche. Considering IgG prevalence according to the province where the BS was located, rates over 30% were found in Sardinia and Abruzzo. Age, sex and donor's region of residence were independently associated with IgG positivity. BS location produced significant heterogeneity on prevalence rates within the regions. DISCUSSION The detected IgG rate of 8.7% in this study represents one of the lowest seroprevalence rates reported among blood donors in Europe. Particularly high prevalence rates in some regions and provinces may be explained by local eating habits and/or intensive environmental HEV contamination. Before considering the introduction of HEV RNA screening for blood donations in Italy, further important issues should be addressed and prospective incidence and reliable cost-benefit studies are needed.
Collapse
|
|
42
|
Al-Sadeq DW, Majdalawieh AF, Mesleh AG, Abdalla OM, Nasrallah GK. Laboratory challenges in the diagnosis of hepatitis E virus. J Med Microbiol 2018; 67:466-480. [PMID: 29485390 DOI: 10.1099/jmm.0.000706] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus that is an important cause of both acute and chronic hepatitis worldwide. To date, there are eight HEV genotypes that can infect mammals. HEV-1 and HEV-2 infect exclusively humans, while HEV-3 and HEV-4 infect humans and various animals, mainly pigs and deer. Additionally, two new genotypes (HEV-5 and HEV-6) infect mainly wild boar. Recently, newly discovered genotypes HEV-7 and HEV-8 were found to infect camels and possibly humans. Nevertheless, the epidemiological distribution of HEV-7 is not well established. HEV-8 is another newly discovered genotype that was identified in 2016 in Chinese Bactrian camels. Although faecal-oral transmission is the most common route of HEV transmission, HEV can be vertically transmitted from infected mothers to their fetuses. HEV may also spread by zoonotic transmission from infected animals to humans and through person-to-person contact. Nowadays, since the number of reported cases linked to blood donations is increasing annually, HEV is recognized as a transfusion-transmitted virus. Laboratory diagnostic techniques vary in their specificity and sensitivity for HEV detection. Direct techniques allow for detection of the viral proteins, antigens and viral nucleic acid, while HEV-specific IgG and IgM antibodies can help establish a diagnosis in acute and chronic infections. In this review, we will discuss recent technologies in the laboratory diagnosis of HEV, including serological and molecular methods to assess the specificity and sensitivity of currently available HEV commercial assays.
Collapse
Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, UAE
| | - Areej G Mesleh
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Omnya M Abdalla
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar.,Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
43
|
O'Gorman J, Burke Á, O'Flaherty N. Hepatitis E virus - key points for the clinical haematologist. Br J Haematol 2018; 181:579-589. [PMID: 29468650 DOI: 10.1111/bjh.15133] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/06/2018] [Indexed: 12/13/2022]
Abstract
In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.
Collapse
Affiliation(s)
- Joanne O'Gorman
- Consultant Clinical Microbiologist, National Virus Reference Laboratory, University College Dublin, Dublin, Ireland
| | - Áine Burke
- Consultant Haematologist, Sligo University Hospital, Sligo, Ireland
| | - Niamh O'Flaherty
- Consultant Clinical Microbiologist, National Virus Reference Laboratory, University College Dublin, Dublin, Ireland.,Consultant Clinical Microbiologist, Irish Blood Transfusion Service, Dublin 8, Ireland
| |
Collapse
|
|
44
|
Izopet J. [HEV and transfusion-recipient risk]. ANNALES PHARMACEUTIQUES FRANÇAISES 2018; 76:89-96. [PMID: 29395014 DOI: 10.1016/j.pharma.2017.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 12/18/2017] [Indexed: 02/06/2023]
Abstract
HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60 % of immunocompromised patients infected with HEV genotype 3. Extra-hepatic manifestations such as neurological and renal manifestations have been reported. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.
Collapse
Affiliation(s)
- J Izopet
- Laboratoire de virologie, centre national de référence virus des hépatites à transmission entérique (hépatites A et E), institut fédératif de biologie, CHU de Purpan, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm U1043/CNRS 5282, université Paul-Sabatier, centre de physiopathologie de Toulouse-Purpan, 31024 Toulouse cedex 03, France.
| |
Collapse
|
|
45
|
Abstract
Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces. However, HEV is increasingly being recognized as endemic in some developed regions. In this setting, infections occur through zoonotic transmission or contaminated blood products and can cause chronic hepatitis in immunocompromised individuals. HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool. Although an effective HEV vaccine exists, it is only licensed for use in China. Acute hepatitis E is usually self-limiting and does not require specific treatment. Management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.
Collapse
|
|
46
|
Al-Sadeq DW, Majdalawieh AF, Nasrallah GK. Seroprevalence and incidence of hepatitis E virus among blood donors: A review. Rev Med Virol 2017; 27:e1937. [PMID: 28876496 DOI: 10.1002/rmv.1937] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/16/2017] [Accepted: 07/18/2017] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.
Collapse
Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
47
|
Hoad VC, Seed CR, Fryk JJ, Harley R, Flower RLP, Hogema BM, Kiely P, Faddy HM. Hepatitis E virus RNA in Australian blood donors: prevalence and risk assessment. Vox Sang 2017; 112:614-621. [PMID: 28833229 DOI: 10.1111/vox.12559] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 06/30/2017] [Accepted: 07/05/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND OBJECTIVES Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.
Collapse
Affiliation(s)
- V C Hoad
- Clinical Services and Research, Australian Red Cross Blood Service, Perth, WA, Australia
| | - C R Seed
- Clinical Services and Research, Australian Red Cross Blood Service, Perth, WA, Australia
| | - J J Fryk
- Research and Development, Australian Red Cross Blood Service, Brisbane, QLD, Australia
| | - R Harley
- Clinical Services and Research, Australian Red Cross Blood Service, Brisbane, QLD, Australia
| | - R L P Flower
- Research and Development, Australian Red Cross Blood Service, Brisbane, QLD, Australia
| | - B M Hogema
- Department of Blood-borne Infections, Sanquin Research, Amsterdam, The Netherlands
| | - P Kiely
- Clinical Services and Research, Australian Red Cross Blood Service, Melbourne, Vic., Australia
| | - H M Faddy
- Research and Development, Australian Red Cross Blood Service, Brisbane, QLD, Australia
| |
Collapse
|
|
48
|
Larralde O, Petrik J. Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid. Med Microbiol Immunol 2017; 206:301-309. [PMID: 28434129 DOI: 10.1007/s00430-017-0507-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 04/17/2017] [Indexed: 12/17/2022]
Abstract
Hepatitis E is an emerging zoonotic infection of increasing public health threat for the UK, especially for immunosuppressed individuals. A human recombinant vaccine has been licensed only in China and is not clear whether it protects against hepatitis E virus (HEV) genotype 3, the most prevalent in Europe. The aim of this study was to use phage display technology as a tool to identify peptides that mimic epitopes of HEV capsid (mimotopes). We identified putative linear and conformational mimotopes using sera from Scottish blood donors that have the immunological imprint of past HEV infection. Four mimotopes did not have homology with the primary sequence of HEV ORF2 capsid but competed effectively with a commercial HEV antigen for binding to anti-HEV reference serum. When the reactivity profile of each mimotope was compared with Wantai HEV-IgG ELISA, the most sensitive HEV immunoassay, mimotopes showed 95.2-100% sensitivity while the specificity ranged from 81.5 to 95.8%. PepSurf algorithm was used to map affinity-selected peptides onto the ORF2 crystal structure of HEV genotype 3, which predicted that these four mimototopes are clustered in the P domain of ORF2 capsid, near conformational epitopes of anti-HEV neutralising monoclonal antibodies. These HEV mimotopes may have potential applications in the design of structural vaccines and the development of new diagnostic tests.
Collapse
Affiliation(s)
- Osmany Larralde
- Microbiology RDI, Scottish National Blood Transfusion Service, NHS National Services Scotland, 21 Ellen's Glen Road, Edinburgh, EH17 7QT, UK.
| | - Juraj Petrik
- Microbiology RDI, Scottish National Blood Transfusion Service, NHS National Services Scotland, 21 Ellen's Glen Road, Edinburgh, EH17 7QT, UK
| |
Collapse
|
|
49
|
Ankcorn MJ, Tedder RS. Hepatitis E: the current state of play. Transfus Med 2017; 27:84-95. [PMID: 28382704 DOI: 10.1111/tme.12405] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/08/2016] [Accepted: 02/22/2017] [Indexed: 12/16/2022]
Abstract
The hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Genotypes 1 and 2 (G1 and G2) are obligate human pathogens transmitted faeco-orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 (G3 and G4) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food-borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self-limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion-transmitted HEV, which has been reported from countries classically considered HEV-endemic but also non-endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.
Collapse
Affiliation(s)
- M J Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| | - R S Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| |
Collapse
|
|
50
|
Early hepatitis E infection in an unrelated hematopoietic progenitor stem cell donor. Bone Marrow Transplant 2017; 52:1471-1472. [PMID: 28714948 DOI: 10.1038/bmt.2017.163] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
|