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Papageorgiou D, de Lastic AL, Tsachouridou O, Metallidis S, Akinosoglou K. HEV Infection in Beta-Thalassemia Patients. Pathogens 2024; 13:1058. [PMID: 39770318 PMCID: PMC11728467 DOI: 10.3390/pathogens13121058] [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: 10/10/2024] [Revised: 11/17/2024] [Accepted: 11/28/2024] [Indexed: 01/14/2025] Open
Abstract
Thalassemia is an inherited hematological disorder characterized by a decrease in the synthesis of or absence of one or more globin chains. Hepatitis E virus (HEV) is a major cause of acute viral hepatitis, constituting a major global health burden and emerging as a critical public health concern. HEV infection is mainly transmitted via the fecal-oral route; however, parenteral transmission through blood components has been reported in both developing and developed countries. Although HEV infection is typically self-limiting, immunocompromised individuals, patients with chronic liver disease, and thalassemic patients are at a heightened risk of contracting the infection and may develop chronic hepatitis and life-threatening complications that require treatment. The reported prevalence rates of HEV in thalassemia patients vary significantly by country. Age, gender, residential area, and the cumulative amount of blood transfusions received have been identified as associated risk factors for HEV infection. In order to enhance blood safety and ensure the protection of vulnerable patient populations, such as thalassemia patients, several countries have introduced universal or targeted HEV screening policies in blood donations. Other preventive measures include vigilant monitoring of thalassemic patients and screening for anti-HEV antibodies. The aim of this review is to explore the prevalence, risk factors, clinical impact and management of HEV infection in patients with thalassemia.
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Affiliation(s)
| | - Anne-Lise de Lastic
- Laboratory of Immunohematology, Medical School, University of Patras, Rio, 26504 Patras, Greece;
| | - Olga Tsachouridou
- Department of Internal Medicine and Infectious Diseases, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Simeon Metallidis
- Department of Internal Medicine and Infectious Diseases, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Karolina Akinosoglou
- Medical School, University of Patras, Rio, 26504 Patras, Greece;
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, Rio, 26504 Patras, Greece
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Antonopoulou N, Schinas G, Kotsiri Z, Tsachouridou O, Protopapas K, Petrakis V, Petrakis EC, Papageorgiou D, Tzimotoudis D, Metallidis S, Papadopoulos A, Marangos M, Barbounakis E, Kofteridis DP, Panagopoulos P, Gogos C, Vantarakis A, Akinosoglou K. Testing Hepatitis E Seroprevalence among HIV-Infected Patients in Greece: The SHIP Study. Pathogens 2024; 13:536. [PMID: 39057763 PMCID: PMC11280285 DOI: 10.3390/pathogens13070536] [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: 04/02/2024] [Revised: 05/26/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024] Open
Abstract
Hepatitis E virus (HEV) poses significant health concerns worldwide, particularly among people living with HIV (PLWHIV), due to an increased risk of chronic infection and progression to cirrhosis in individuals with low CD4 cell counts. This study aimed to investigate the prevalence, chronicity potential, and risk factors of HEV infection among PLWHIV in Greece, where data are currently absent. A synchronic multicentric study encompassing five major Greek university hospitals was executed over 24 months, recruiting 696 PLWHIV participants. The prevalence of HEV IgG antibodies was 16.5%, with 8.6% showing evidence of acute HEV infection (HEV IgM). Active viral replication (HEV RNA) was present in 2.3% of the study population. Longitudinal analysis revealed that of the 25 initially anti-HEV IgM-positive individuals, only 3 seroconverted to IgG positivity, and among those with prior HEV RNA positivity (16), none showed evidence of active replication in subsequent tests. Comparative subgroup analysis highlighted the lack of significant differences in HIV-related parameters between HEV seropositive and seronegative individuals. Laboratory evaluations generally showed no significant disparities across most parameters; however, a higher seropositivity for Hepatitis A was observed in the HEV-positive subgroup. Our findings highlight a considerable prevalence of HEV among PLWHIV in Greece, with no observed cases of chronicity.
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Affiliation(s)
- Nikolina Antonopoulou
- Department of Internal Medicine and Infectious Diseases, University of Patras, 26504 Patras, Greece; (N.A.); (M.M.)
| | - Georgios Schinas
- School of Medicine, University of Patras, 26504 Patras, Greece; (G.S.); (D.P.); (C.G.)
| | - Zoi Kotsiri
- Department of Public Health, University of Patras, 26504 Patras, Greece; (Z.K.); (D.T.); (A.V.)
| | - Olga Tsachouridou
- Department of Internal Medicine and Infectious Diseases AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Konstantinos Protopapas
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, 12462 Athens, Greece; (K.P.); (A.P.)
| | - Vasileios Petrakis
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (V.P.); (P.P.)
| | - Emmanouil C. Petrakis
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Heraklion, University of Crete, 71500 Heraklion, Greece; (E.C.P.); (E.B.); (D.P.K.)
| | - Despoina Papageorgiou
- School of Medicine, University of Patras, 26504 Patras, Greece; (G.S.); (D.P.); (C.G.)
| | - Dimosthenis Tzimotoudis
- Department of Public Health, University of Patras, 26504 Patras, Greece; (Z.K.); (D.T.); (A.V.)
| | - Simeon Metallidis
- Department of Internal Medicine and Infectious Diseases AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Antonios Papadopoulos
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, 12462 Athens, Greece; (K.P.); (A.P.)
| | - Markos Marangos
- Department of Internal Medicine and Infectious Diseases, University of Patras, 26504 Patras, Greece; (N.A.); (M.M.)
- School of Medicine, University of Patras, 26504 Patras, Greece; (G.S.); (D.P.); (C.G.)
| | - Emmanouil Barbounakis
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Heraklion, University of Crete, 71500 Heraklion, Greece; (E.C.P.); (E.B.); (D.P.K.)
| | - Diamantis P. Kofteridis
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Heraklion, University of Crete, 71500 Heraklion, Greece; (E.C.P.); (E.B.); (D.P.K.)
| | - Periklis Panagopoulos
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (V.P.); (P.P.)
| | - Charalambos Gogos
- School of Medicine, University of Patras, 26504 Patras, Greece; (G.S.); (D.P.); (C.G.)
| | - Apostolos Vantarakis
- Department of Public Health, University of Patras, 26504 Patras, Greece; (Z.K.); (D.T.); (A.V.)
| | - Karolina Akinosoglou
- Department of Internal Medicine and Infectious Diseases, University of Patras, 26504 Patras, Greece; (N.A.); (M.M.)
- School of Medicine, University of Patras, 26504 Patras, Greece; (G.S.); (D.P.); (C.G.)
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Capai L, Masse S, Hozé N, Decarreaux D, Canarelli J, Simeoni MH, de Lamballerie X, Falchi A, Charrel R. Seroprevalence of anti-HEV IgG in children: very early exposure in young children in a hyperendemic region. Front Public Health 2023; 11:1293575. [PMID: 38026418 PMCID: PMC10680972 DOI: 10.3389/fpubh.2023.1293575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Background and objectives Hepatitis E virus (HEV) can be considered an emerging zoonotic pathogen and is an important cause of acute viral hepatitis in high-income countries. Corsica has been identified as a hyperendemic region for HEV. We aimed to characterize the prevalence of IgG among children and estimate the annual force of infection of HEV. Methods From April 2020 to June 2021, we collected 856 "residual sera" in 13 medical biology laboratories. Sera were tested using the Wantaï HEV IgG assay. Data were weighted according to the distribution by sex and age of the real Corsican population. Serocatalytic models were applied to assess the annual force of infection of HEV. Results The weighted seroprevalence was 30.33% [27.15-34.0]. The seroprevalence was only associated with increasing age (7.25-40.52%; p < 0.001). The annual probability of infection was 5.4% for adults and children above 10-year-old and 2.2% for children under 10 yo. Conclusion Our study demonstrates that in the hyperendemic island of Corsica, (i) exposure of the population to HEV is homogeneous at the spatial level with no difference between genders; (ii) HEV exposure occurs from birth, resulting in 7.4% seropositivity at the age of 4 years; and (iii) super exposure is observed after the age of 9 years. Accordingly, specific studies should be conducted to determine the breadth of the situation identified in our study. The role of the environment and its contamination by domestic or wild swine excreta should be investigated using a One Health approach.
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Affiliation(s)
- Lisandru Capai
- UR 7310, Université de Corse, Corte, France
- AG Junglen, Institute of Virology, University of Charité, Berlin, Germany
| | | | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France
| | - Dorine Decarreaux
- UR 7310, Université de Corse, Corte, France
- Unité des Virus Émergents, Aix-Marseille University, Marseille, France
| | | | | | | | | | - Rémi Charrel
- Unité des Virus Émergents, Aix-Marseille University, Marseille, France
- Comité de Lutte contre les infections Nosocomiales, APHM HOPITAUX Universitaires de Marseille, Marseille, France
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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.
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Raji YE, Toung OP, Taib NM, Sekawi ZB. Hepatitis E Virus: An emerging enigmatic and underestimated pathogen. Saudi J Biol Sci 2022; 29:499-512. [PMID: 35002446 PMCID: PMC8716866 DOI: 10.1016/j.sjbs.2021.09.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 08/31/2021] [Accepted: 09/05/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 - 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re - emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.
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Affiliation(s)
- Yakubu Egigogo Raji
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
- Faculty of Natural and Applied Sciences Ibrahim Badamasi Babangida University, Lapai, Nigeria
| | - Ooi Peck Toung
- Department of Veterinary Clinical Studies Faculty of Veterinary Medicine, Universiti Putra Malaysia 2, Malaysia
| | - Niazlin Mohd Taib
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
| | - Zamberi Bin Sekawi
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
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Mrzljak A, Jemersic L, Savic V, Balen I, Ilic M, Jurekovic Z, Pavicic-Saric J, Mikulic D, Vilibic-Cavlek T. Hepatitis E Virus in Croatia in the "One-Health" Context. Pathogens 2021; 10:699. [PMID: 34199798 PMCID: PMC8227679 DOI: 10.3390/pathogens10060699] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/01/2021] [Accepted: 06/02/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.
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Affiliation(s)
- Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Lorena Jemersic
- Department of Virology, Croatian Veterinary Institute, 10000 Zagreb, Croatia;
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia;
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, 35000 Slavonski Brod, Croatia;
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia;
| | - Zeljka Jurekovic
- Department of Medicine, Merkur University Hospital, 10000 Zagreb, Croatia;
| | - Jadranka Pavicic-Saric
- Department of Anestesiology, Reanimatology and Intensive Care, Merkur University Hospital, 10000 Zagreb, Croatia;
| | - Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, 10000 Zagreb, Croatia;
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia
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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.
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Seroprevalence Study of Anti-HEV IgG among Different Adult Populations in Corsica, France, 2019. Microorganisms 2019; 7:microorganisms7100460. [PMID: 31623185 PMCID: PMC6843757 DOI: 10.3390/microorganisms7100460] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 09/19/2019] [Accepted: 10/15/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. In France, hyperendemic areas including Corsica have an anti-HEV Immunoglobulin G (IgG) prevalence higher than 50%. The aim of this study was to determine the seroprevalence of anti-HEV IgG in three adult populations in Corsica and the risk factors associated with antibody detection. Between 2017 and 2019, a total of 930 individuals, including 467 blood donors, 393 students or university staff members and 70 patients from general practice, were tested for the presence of anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay kit and filled a questionnaire. The association between seropositivity and potential risk factors was tested with univariate and multivariate analyses. Out of the 930 samples, 52.3% (486/930) were seropositive—54.4% (254/467) among blood donors, 47.6% (187/393) among university students and 64.3% (45/70) among patients of general practice. Three main risk factors were identified: (i) skinning and butchering (Adjusted Odds Ratio aOR = 2.76, 95% confidence interval [95% CI] [1.51–5.37]; p-value < 10−3), (ii) consumption of a local pork live raw sausage (fittonu) (aOR = 1.95 95% CI [1.45–2.64]; p-value = 10−5), and (iii) increasing age (p-value = 0.003). Seropositivity rates between the different populations were homogeneous after age stratification. This cross-sectional study indicates a high anti-HEV IgG seroprevalence in the Corsican adult population, not significantly different between women and men and increasing with age. This serosurvey also showed homogeneity regarding the exposure to HEV among three different types of populations. Finally, we confirmed the endemicity of Corsica with respect to HEV and identified a strong association between consumption of figatellu/fittonu and the practice of skinning and butchering with the detection of anti-HEV IgG.
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Mrzljak A, Dinjar-Kujundzic P, Jemersic L, Prpic J, Barbic L, Savic V, Stevanovic V, Vilibic-Cavlek T. Epidemiology of hepatitis E in South-East Europe in the "One Health" concept. World J Gastroenterol 2019; 25:3168-3182. [PMID: 31333309 PMCID: PMC6626717 DOI: 10.3748/wjg.v25.i25.3168] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/16/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023] Open
Abstract
The significance of hepatitis E virus (HEV) as an important public health problem is rising. Until a decade ago, cases of HEV infection in Eur-ope were mainly confined to returning travelers, but nowadays, hepatitis E represents an emerging zoonotic infection in many European countries. The aim of this manuscript is to perform a systematic review of the published literature on hepatitis E distribution in humans, animals and environmental samples ("One Health" concept) in the South-Eastern European countries. Comparison of the available data showed that the anti-HEV seroprevalence in the South-Eastern Europe varies greatly, depending on the population studied, geographical area and methods used. The IgG seroprevalence rates in different population groups were found to be 1.1%-24.5% in Croatia, up to 20.9% in Bulgaria, 5.9-%17.1% in Romania, 15% in Serbia, up to 9.7% in Greece and 2%-9.7% in Albania. Among possible risk factors, older age was the most significant predictor for HEV seropositivity in most studies. Higher seroprevalence rates were found in animals. HEV IgG antibodies in domestic pigs were detected in 20%-54.5%, 29.2%-50%, 38.94%-50% and 31.1%-91.7% in Serbia, Bulgaria, Romania and Croatia, respectively. In wild boars seroprevalence rates were up to 10.3%, 30.3% and 31.1% in Romania, Slovenia and Croatia, respectively. A high HEV RNA prevalence in wild boars in some countries (Croatia and Romania) indicated that wild boars may have a key role in the HEV epidemiology. There are very few data on HEV prevalence in environmental samples. HEV RNA was detected in 3.3% and 16.7% surface waters in Slovenia and Serbia, respectively. There is no evidence of HEV RNA in sewage systems in this region. The available data on genetic characterization show that human, animal and environmental HEV strains mainly belong to the genotype 3.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | | | - Lorena Jemersic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Jelena Prpic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | - Vladimir Savic
- Croatian Veterinary Institute, Zagreb 10000, Grad Zagreb, Croatia
| | - Vladimir Stevanovic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Grad Zagreb, Croatia
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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.
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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
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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.
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Klonizakis P, Gioula G, Exindari M, Apostolou C, Kotsiafti A, Vlachaki E. Hepatitis E in transfusion-dependent thalassaemia patients, in Greece: a single centre experience. Vox Sang 2017; 112:678-679. [PMID: 28891120 DOI: 10.1111/vox.12572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Revised: 08/06/2017] [Accepted: 08/07/2017] [Indexed: 12/23/2022]
Abstract
Hepatitis E is considered an emerging disease that may be a threat in both developing and industrialized countries all over the world. The risk of chronic hepatitis E virus infection is higher among immunocompromised patients. This study aimed to assess the status of hepatitis E infection in patients with transfusion-dependent thalassaemia from a single centre, in Greece. Our results suggest that the prevalence of hepatitis E infection in this group of patients is low.
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Affiliation(s)
- P Klonizakis
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - G Gioula
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - M Exindari
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - C Apostolou
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - A Kotsiafti
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - E Vlachaki
- School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Hepatitis E Virus in Industrialized Countries: The Silent Threat. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9838041. [PMID: 28070522 PMCID: PMC5192302 DOI: 10.1155/2016/9838041] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/07/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) is the main cause of acute viral hepatitis worldwide. Its presence in developing countries has been documented for decades. Developed countries were supposed to be virus-free and initially only imported cases were detected in those areas. However, sporadic and autochthonous cases of HEV infection have been identified and studies reveal that the virus is worldwide spread. Chronic hepatitis and multiple extrahepatic manifestations have also been associated with HEV. We review the data from European countries, where human, animal, and environmental data have been collected since the 90s. In Europe, autochthonous HEV strains were first detected in the late 90s and early 2000s. Since then, serological data have shown that the virus infects quite frequently the European population and that some species, such as pigs, wild boars, and deer, are reservoirs. HEV strains can be isolated from environmental samples and reach the food chain, as shown by the detection of the virus in mussels and in contaminated pork products as sausages or meat. All these data highlight the need of studies directed to control the sources of HEV to protect immunocompromised individuals that seem the weakest link of the HEV epidemiology in industrialized regions.
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Behloul N, Zhang M, Meng J. Binding Preference of Anti-HEV Antibodies in Sera Collected in Algeria for Antigens Derived From HEV Genotype 1. HEPATITIS MONTHLY 2016; 16:e35312. [PMID: 27795723 PMCID: PMC5070561 DOI: 10.5812/hepatmon.35312] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 02/26/2016] [Accepted: 05/10/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Two hepatitis E virus (HEV) outbreaks occurred in Algeria (1979 - 1980 and 1987 - 1988). However, to date, no study on the prevalence of anti-HEV antibodies has been conducted in Algeria, and the genotype of the circulating strains remains unclear. OBJECTIVES This study was conducted to investigate the presence of anti- HEV antibodies among outpatients and blood donors in three different hospitals in Northern Algeria and to determine the genotype of the circulating strains through the characterization of the immunoreactivity of anti-HEV antibodies. METHODS A total of 590 blood samples (379 from blood donors and 211 from outpatients) were collected in three health facilities in Northern Algeria and assessed for anti-HEV antibodies using an in-house double-antigen sandwich immunoassay. HEV open reading frame 2 recombinant proteins p166 (aa 452 - 617) generated from the four HEV genotypes were used as antigens. The genotype of the strains circulating in Algeria was predicted by an indirect ELISA by assessing the anti-HEV antibodies in serially diluted positive sera using the different p166 proteins. RESULTS Anti-HEV antibodies were detected in 20.17% of the samples. A significant correlation was found between the age of the subjects and the presence of anti-HEV antibodies (P < 0.001). Among blood donors, 83 (21.9%) were diagnosed positive for anti-HEV antibodies with two cases weakly positive for anti-HEV IgM antibodies. Moreover, 9.9% of the subjects aged less than 25 years old (born after the last HEV outbreak) were positive for anti-HEV antibodies. The indirect ELISA revealed that the anti-HEV antibodies within the positive sera reacted more strongly against the p166 antigens generated from genotype 1. CONCLUSIONS The present findings reveal a relatively high presence of anti-HEV IgGs and clearly indicate that HEV infection is still present in Northern Algeria. Further, the prediction of HEV genotype using different antigens generated from the different HEV genotypes shows that the causative strains are more likely to be of genotype 1.
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Affiliation(s)
- Nouredine Behloul
- Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China
| | - Min Zhang
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jihong Meng
- Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China
- Corresponding Author: Jihong Meng, Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China. Tel/Fax: +86-2583272386, E-mail:
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Hoan NX, Tong HV, Hecht N, Sy BT, Marcinek P, Meyer CG, Song LH, Toan NL, Kurreck J, Kremsner PG, Bock CT, Velavan TP. Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients. EBioMedicine 2015; 2:2080-2086. [PMID: 26844288 PMCID: PMC4703726 DOI: 10.1016/j.ebiom.2015.11.020] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 10/21/2015] [Accepted: 11/10/2015] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease.
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Key Words
- AFP, alpha-feto protein
- AHB, acute hepatitis B
- ALT, alanine amino transferase
- AST, aspartate amino transferase
- CHB, chronic hepatitis B
- HBV infection
- HBV, hepatitis B virus
- HBV-related liver diseases
- HCC, hepatocellular carcinoma
- HEV seroprevalence
- HEV superinfection
- HEV, hepatitis E virus
- Hepatitis E virus
- IgG, immunoglobulin G
- IgM, immunoglobulin M
- LC, liver cirrhosis
- ORF, open reading frame
- PLT, platelets
- RBC, red blood cells
- WBC, white blood cells
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Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Hoang Van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Nicole Hecht
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Bui Tien Sy
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- Department of Molecular Biology, Tran Hung Dao Hospital, Hanoi, Viet Nam
| | - Patrick Marcinek
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Christian G. Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, Tran Hung Dao Hospital, Hanoi, Viet Nam
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Ha Dong, Hanoi, Viet Nam
| | - Jens Kurreck
- Department of Biotechnology, Technical University of Berlin, Berlin, Germany
| | - Peter G. Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - C-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
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Sayed IM, Vercauteren K, Abdelwahab SF, Meuleman P. The Emergence of Hepatitis E Virus in Europe. Future Virol 2015; 10:763-778. [DOI: 10.2217/fvl.15.29] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Ibrahim M Sayed
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
- Microbiology & Immunology Department, Faculty of Medicine, Assuit University, Assuit71515, Egypt
| | - Koen Vercauteren
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
| | - Sayed F Abdelwahab
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia61511, Egypt
| | - Philip Meuleman
- Center for Vaccinology, Ghent University, Ghent University Hospital, B-9000Gent, Belgium
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Politou M, Boti S, Androutsakos T, Valsami S, Pittaras T, Kapsimali V. Seroprevalence of hepatitis E in HIV infected patients in Greece. J Med Virol 2015; 87:1517-20. [PMID: 25965115 DOI: 10.1002/jmv.24214] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2015] [Indexed: 12/23/2022]
Abstract
HEV infection is an emerging public health problem worldwide Data concerning HEV infection in HIV+ patients in Greece is scare. The aim of the study was to determine HEV seroprevalence in patients with HIV infection in Greece. We studied 243 HIV(+) patients 214 men (88%) and 29 women (12%) with a median age of 45 years (range 19-83) who attended the HIV unit of Pathophysiology Department of Laikon General Hospital in Athens for the presence of anti-HEV IgG antibodies with (EIA) (EIA HEV IgG, Adaltis, Rome, Italy Eighteen/243 patients (7.3%) were positive for HEV IgG antibodies, a seroprevalence that was not different from that described for the blood donors group from Greece There was no difference of the presence of HbsAg, hepatitis C and hepatitis A between the HEV(+) and HEV(-) patients. There was no statistically significant difference between the HEV(+) and HEV(-) group in terms of HIV acquisition, sexual orientation, median duration of HIV infection, ART treatment, or duration of ART. Only the median age of HEV(+) was 52 years (35-78) while that of HEV(-) was 44 years (19-83)(P = 0.03). Only 2/18(11.1%) HEV(+) HIV(+) patients had abnormal ALT and AST values. The seroprevalence of hepatitis E in HIV(+) patients in Greece seems to be the same with that of the general population thus implying that HIV infection is not a risk factor for HEV infection and only age shows a positive correlation with seropositivity.
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Affiliation(s)
- Marianna Politou
- Hematology Laboratory, Blood Bank, Aretaieion Hospital, Athens, Greece
| | - Sofia Boti
- AIDS Unit, Pathophysiology Clinic, Laikon Hospital, Athens, Greece
| | | | - Serena Valsami
- Hematology Laboratory, Blood Bank, Aretaieion Hospital, Athens, Greece
| | - Theodoros Pittaras
- Microbiology Laboratory, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Violetta Kapsimali
- Microbiology Laboratory, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Sauleda S, Ong E, Bes M, Janssen A, Cory R, Babizki M, Shin T, Lindquist A, Hoang A, Vang L, Piron M, Casamitjana N, Koppelman M, Danzig L, Linnen JM. Seroprevalence of hepatitis E virus (HEV) and detection of HEV RNA with a transcription-mediated amplification assay in blood donors from Catalonia (Spain). Transfusion 2014; 55:972-9. [PMID: 25403913 DOI: 10.1111/trf.12929] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 09/17/2014] [Accepted: 09/20/2014] [Indexed: 01/10/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is an emerging threat to the safety of blood transfusion. The aim of this study was to determine HEV immunoglobulin (Ig)G and RNA prevalence in Catalan blood donors. STUDY DESIGN AND METHODS Nearly 10,000 samples were collected from anonymized, unpaid donors at the Banc de Sang i Teixits (Barcelona, Spain) from June to December 2013. For the serology study, a subset of 1082 donations was tested in parallel for HEV IgG using Wantai and Mikrogen enzyme-linked immunosorbent assay tests. Samples were tested individually (individual-donation nucleic acid test [ID-NAT]) for HEV RNA using the Procleix HEV assay (95% limit of detection 7.9 IU/mL). Procleix repeat-reactive donations were confirmed by an in-house real-time polymerase chain reaction (PCR) test. RESULTS The prevalences of IgG anti-HEV in Catalan blood donors were 19.96% (Wantai assay) and 10.72% (Mikrogen assay). Screening of 9998 samples with the Procleix HEV assay yielded three real-time PCR-confirmed and IgM and IgG anti-HEV-positive donations with viral loads of 250, 564, and 2755 IU/mL. The donation with highest viral load was genotype 3f. HEV RNA positivity rate was one per 3333 donations (0.03%; 95% confidence interval, 0.01%-0.09%). CONCLUSION The Procleix HEV ID-NAT screening system has provided evidence of HEV RNA presence in Catalan blood donors. Further data are needed to assess the impact of HEV infection in at-risk patients to design the best strategy to increase blood safety.
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Affiliation(s)
- Sílvia Sauleda
- Transfusion Safety Laboratory, Banc de Sang i Teixits, Institut Català de la Salut, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Edgar Ong
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Marta Bes
- Transfusion Safety Laboratory, Banc de Sang i Teixits, Institut Català de la Salut, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Alanna Janssen
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Robin Cory
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Maria Babizki
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Tim Shin
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Andre Lindquist
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Anh Hoang
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Lee Vang
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
| | - Maria Piron
- Transfusion Safety Laboratory, Banc de Sang i Teixits, Institut Català de la Salut, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Natàlia Casamitjana
- Transfusion Safety Laboratory, Banc de Sang i Teixits, Institut Català de la Salut, Barcelona, Spain
| | - Marco Koppelman
- Sanquin Diagnostics, National Screening Laboratory of Sanquin (NSS), Amsterdam, the Netherlands
| | - Lisa Danzig
- Grifols (formerly Novartis Diagnostics), Emeryville, California
| | - Jeffrey M Linnen
- Hologic, Inc. (formerly Gen-Probe Incorporated), San Diego, California
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Hepatitis E: an old infection with new implications. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2014; 13:6-17. [PMID: 25369613 DOI: 10.2450/2014.0063-14] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 06/18/2014] [Indexed: 12/24/2022]
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