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Bagulo H, Majekodunmi AO, Welburn SC, Bimi L. The burden of hepatitis E virus infection among Ghanaian pregnant women. Front Public Health 2025; 12:1507488. [PMID: 39845687 PMCID: PMC11752893 DOI: 10.3389/fpubh.2024.1507488] [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: 10/07/2024] [Accepted: 12/03/2024] [Indexed: 01/24/2025] Open
Abstract
Introduction Hepatitis E virus (HEV) infection poses a significant burden on pregnant women, with associated negative outcomes. Although well-described in many developed countries, the epidemiology of the disease and its impact on maternal and fetal health in Ghana is not fully understood. Materials and methods A cross-sectional survey was conducted in the antenatal clinics of 10 district hospitals in five regions of Ghana. The study involved 1,000 pregnant women attending antenatal care. Serological and virological assays were employed to determine HEV seroprevalence and prevalence. Logistic regression analysis was carried out in univariate and multivariate models to assess risk factors associated with HEV infection. Results HEV-Immunoglobulin G (IgG) seroprevalence of 8.3% was recorded among the pregnant women with 1% HEV-antigen prevalence. However, none were positive for HEV-IgM and HEV RNA. 19.8% of the pregnant women reported poor pregnancy outcomes in previous pregnancies. Age, educational attainment, and region were significant predictors of HEV IgG seropositivity in the univariate regression model, while age and region were the only significant predictors in a multivariate model. Also, the drinking water source and the toilet type accurately predicted HEV IgG seroprevalence in both univariate and multivariate models. Discussion Pregnancy care must be significantly improved to reduce maternal and foetal morbidity and mortality.
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Affiliation(s)
- Husein Bagulo
- Zhejiang University – University of Edinburgh Institute, Haining, Zhejiang, China
- School of Biomedical Sciences, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
| | - Ayodele O. Majekodunmi
- School of Biomedical Sciences, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
- Food and Agriculture Organisation of the United Nations, Garki, Abuja, Nigeria
| | - Susan C. Welburn
- Zhejiang University – University of Edinburgh Institute, Haining, Zhejiang, China
- School of Biomedical Sciences, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
| | - Langbong Bimi
- Department of Animal Biology and Conservation Science, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana
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Shun EHK, Situ J, Tsoi JYH, Wu S, Cai J, Lo KHY, Chew NFS, Li Z, Poon RWS, Teng JLL, Cheng VCC, Yuen KY, Sridhar S. Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong. Emerg Microbes Infect 2024; 13:2337671. [PMID: 38551320 PMCID: PMC11018080 DOI: 10.1080/22221751.2024.2337671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/27/2024] [Indexed: 04/06/2024]
Abstract
Hepatitis E virus (HEV) variants infecting humans belong to two species: Paslahepevirus balayani (bHEV) and Rocahepevirus ratti (rat hepatitis E virus; rHEV). R. ratti is a ubiquitous rodent pathogen that has recently been recognized to cause hepatitis in humans. Transmission routes of rHEV from rats to humans are currently unknown. In this study, we examined rHEV exposure in cats and dogs to determine if they are potential reservoirs of this emerging human pathogen. Virus-like particle-based IgG enzymatic immunoassays (EIAs) capable of differentiating rHEV & bHEV antibody profiles and rHEV-specific real-time RT-PCR assays were used for this purpose. The EIAs could detect bHEV and rHEV patient-derived IgG spiked in dog and cat sera. Sera from 751 companion dogs and 130 companion cats in Hong Kong were tested with these IgG enzymatic immunoassays (EIAs). Overall, 13/751 (1.7%) dogs and 5/130 (3.8%) cats were sero-reactive to HEV. 9/751 (1.2%) dogs and 2/130 (1.5%) cats tested positive for rHEV IgG, which was further confirmed by rHEV immunoblots. Most rHEV-seropositive animals were from areas in or adjacent to districts reporting human rHEV infection. Neither 881 companion animals nor 652 stray animals carried rHEV RNA in serum or rectal swabs. Therefore, we could not confirm a role for cats and dogs in transmitting rHEV to humans. Further work is required to understand the reasons for low-level seropositivity in these animals.
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Affiliation(s)
- Estie Hon-Kiu Shun
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - James Yiu-Hung Tsoi
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jianpiao Cai
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Kelvin Hon-Yin Lo
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Zhiyu Li
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Rosana Wing-Shan Poon
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jade Lee-Lee Teng
- Faculty of Dentistry, The University of Hong Kong, Hong Kong, People’s Republic of China
| | - Vincent Chi-Chung Cheng
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Kwok-Yung Yuen
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
- Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, People’s Republic of China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, People’s Republic of China
- Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
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Piña A, Elko EA, Caballero R, Metrailer M, Mulrow M, Quan D, Nordstrom L, Altin JA, Ladner JT. Mapping disparities in viral infection rates using highly multiplexed serology. mSphere 2024; 9:e0012724. [PMID: 39162531 PMCID: PMC11423740 DOI: 10.1128/msphere.00127-24] [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: 02/19/2024] [Accepted: 07/21/2024] [Indexed: 08/21/2024] Open
Abstract
Despite advancements in medical interventions, the disease burden caused by viral pathogens remains large and highly diverse. This burden includes the wide range of signs and symptoms associated with active viral replication as well as a variety of clinical sequelae of infection. Moreover, there is growing evidence supporting the existence of sex- and ethnicity-based health disparities linked to viral infections and their associated diseases. Despite several well-documented disparities in viral infection rates, our current understanding of virus-associated health disparities remains incomplete. This knowledge gap can be attributed, in part, to limitations of the most commonly used viral detection methodologies, which lack the breadth needed to characterize exposures across the entire virome. Additionally, virus-related health disparities are dynamic and often differ considerably through space and time. In this study, we utilize PepSeq, an approach for highly multiplexed serology, to broadly assess an individual's history of viral exposures, and we demonstrate the effectiveness of this approach for detecting infection disparities through a pilot study of 400 adults aged 30-60 in Phoenix, AZ. Using a human virome PepSeq library, we observed expected seroprevalence rates for several common viruses and detected both expected and previously undocumented differences in inferred rates of infection between our male/female and Hispanic/non-Hispanic White individuals. IMPORTANCE Our understanding of population-level virus infection rates and associated health disparities is incomplete. In part, this is because of the high diversity of human-infecting viruses and the limited breadth and sensitivity of traditional approaches for detecting infection events. Here, we demonstrate the potential for modern, highly multiplexed antibody detection methods to greatly increase our understanding of disparities in rates of infection across subpopulations (e.g., different sexes or ethnic groups). The use of antibodies as biomarkers allows us to detect evidence of past infections over an extended period, and our approach for highly multiplexed serology (PepSeq) allows us to measure antibody responses against hundreds of viruses in an efficient and cost-effective manner.
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Affiliation(s)
- Alejandra Piña
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, USA
| | - Evan A Elko
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, USA
| | | | - Morgan Metrailer
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, USA
| | | | - Dan Quan
- Valleywise Health, Phoenix, Arizona, USA
- University of Arizona, College of Medicine, Phoenix, Arizona, USA
- Creighton University, School of Medicine, Phoenix, Arizona, USA
| | | | - John A Altin
- The Translational Genomics Research Institute (TGen), Flagstaff, Arizona, USA
| | - Jason T Ladner
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, USA
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Letafati A, Taghiabadi Z, Roushanzamir M, Memarpour B, Seyedi S, Farahani AV, Norouzi M, Karamian S, Zebardast A, Mehrabinia M, Ardekani OS, Fallah T, Khazry F, Daneshvar SF, Norouzi M. From discovery to treatment: tracing the path of hepatitis E virus. Virol J 2024; 21:194. [PMID: 39180020 PMCID: PMC11342613 DOI: 10.1186/s12985-024-02470-3] [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: 05/05/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.
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Affiliation(s)
- Arash Letafati
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
| | - Zahra Taghiabadi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mahshid Roushanzamir
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pharmacological and Biomolecular Science, University of Milan, Milan, Italy
| | - Bahar Memarpour
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Masoomeh Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saeideh Karamian
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arghavan Zebardast
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Mehrabinia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Tina Fallah
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Khazry
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Samin Fathi Daneshvar
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
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Bienz M, Renaud C, Liu JR, Wong P, Pelletier P. Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening? Transfus Med Rev 2024; 38:150835. [PMID: 39059853 DOI: 10.1016/j.tmrv.2024.150835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/14/2024] [Accepted: 04/17/2024] [Indexed: 07/28/2024]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
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Affiliation(s)
- Marc Bienz
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
| | - Christian Renaud
- Department of Microbiology, Infectious diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada; Medical Affairs and Innovation, Héma-Québec, Montreal, Quebec, Canada
| | - Jia Ru Liu
- Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Philip Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Patricia Pelletier
- Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada
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Zahmanova G, Takova K, Lukov GL, Andonov A. Hepatitis E Virus in Domestic Ruminants and Virus Excretion in Milk-A Potential Source of Zoonotic HEV Infection. Viruses 2024; 16:684. [PMID: 38793568 PMCID: PMC11126035 DOI: 10.3390/v16050684] [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: 03/27/2024] [Revised: 04/21/2024] [Accepted: 04/23/2024] [Indexed: 05/26/2024] Open
Abstract
The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.
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Affiliation(s)
- Gergana Zahmanova
- Department of Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Georgi L. Lukov
- Faculty of Sciences, Brigham Young University–Hawaii, Laie, HI 96762, USA
| | - Anton Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;
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Viral agents (2nd section). Transfusion 2024; 64 Suppl 1:S19-S207. [PMID: 38394038 DOI: 10.1111/trf.17630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024]
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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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Rivero MA, Arce LP, Gutiérrez SE, Tisnés A, Passucci JA, Silva JA, Barón Prato A, Sánchez F, Matias Brancher J, Estein SM, Vizoso-Pinto MG. Exploring hepatitis E virus seroprevalence and associated risk factors among the human population in Tandil, Buenos Aires, Argentina. Front Public Health 2023; 11:1257754. [PMID: 37869189 PMCID: PMC10585172 DOI: 10.3389/fpubh.2023.1257754] [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: 07/12/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Background Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide and is emerging as a disease in Argentina. It is primarily transmitted through contaminated water and food, following the fecal-oral route. Furthermore, is a zoonotic disease with swine as the primary reservoir. Prevalence of HEV infection in humans in several regions of Argentina remains unknown. Objectives (i) Determine the seroprevalence of HEV among the human population in Tandil, Buenos Aires, Argentina; (ii) Evaluate its association with demographic, socioeconomic and other risk exposures variables, and (iii) Describe and analyze spatial patterns related to HEV infection. Methods From August 2020 to July 2021, serum samples were collected from 969 individuals aged 1-80 years. Seroprevalence and 95% Confidence Interval was determined. To assess the factors associated with the presence of anti-HEV antibodies, associations between the variables and seropositivity were evaluated through bivariate and multivariate analysis. Spatial scanning for clusters of positivity was carried out. Factors associated with these clusters were also assessed. Results Anti-HEV antibodies were detected in 4.64% (IC 95% 3.27-6.02) of samples. Dark urine was associated with seropositivity (p = 0.02). Seropositivity was linked with the presence of natural water courses near their households (p = 0.02); the age (p = 0.04); and previous travel to Europe (p = 0.04). A spatial cluster of low rates of HEV seropositivity was detected, with greater distance of the households to water courses associated to the cluster, and male sex inversely associated to it. Discussion and conclusion This study is the first study to investigate the prevalence of HEV in the population from Tandil, Buenos Aires, Argentina. Considering HEV infection in the differential diagnosis in individuals presenting acute hepatitis is highlighted. The incorporation of HEV testing into blood screening policies should be mandatory. Factors related to the infection and spatial patterns of high and low risk were determined, and should be considered when implementing specific preventive measures.
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Affiliation(s)
- Mariana Alejandra Rivero
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Lorena Paola Arce
- Laboratorio de Biología de las Infecciones, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Tucumán, Argentina
- Laboratorio de Ciencias Básicas Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Silvina Elena Gutiérrez
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Adela Tisnés
- Facultad de Ciencias Humanas, CIG- IGEHCS- CONICET, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Juan Antonio Passucci
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Julia Analia Silva
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Ayelén Barón Prato
- Facultad de Ciencias Humanas, CIG- IGEHCS- CONICET, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Florencia Sánchez
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - Julia Matias Brancher
- Laboratorio de Ciencias Básicas Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Silvia Marcela Estein
- Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Tandil, Argentina
| | - María Guadalupe Vizoso-Pinto
- Laboratorio de Biología de las Infecciones, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Tucumán, Argentina
- Laboratorio de Ciencias Básicas Or. Genética, Facultad de Medicina de la Universidad Nacional de Tucumán, Tucumán, Argentina
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Sakulsaengprapha V, Wasuwanich P, Thawillarp S, Ingviya T, Phimphilai P, Sue PK, Jackson AM, Kraus ES, Teshale EH, Kamili S, Karnsakul W. Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States. Transpl Immunol 2023; 78:101809. [PMID: 36863665 DOI: 10.1016/j.trim.2023.101809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/24/2023] [Accepted: 02/26/2023] [Indexed: 03/04/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012. METHODS HEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection. RESULTS Out of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81-57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04-0.90; p = 0.046). CONCLUSION KTRs who had HEV infection may be at an increased risk of developing chronic HEV.
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Affiliation(s)
| | - Paul Wasuwanich
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Supharerk Thawillarp
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Thammasin Ingviya
- Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA
| | | | - Paul K Sue
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Edward S Kraus
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eyasu H Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, GA, USA
| | - Saleem Kamili
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, GA, USA
| | - Wikrom Karnsakul
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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11
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Animal Models for Studying Congenital Transmission of Hepatitis E Virus. Microorganisms 2023; 11:microorganisms11030618. [PMID: 36985191 PMCID: PMC10057890 DOI: 10.3390/microorganisms11030618] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/05/2023] Open
Abstract
One of the most intriguing issues in the hepatitis E virus (HEV) field is the significant increase in mortality rates of the mother and fetus when infection occurs in the second and third trimesters of gestation. A virus that is normally self-limiting and has a mortality rate of less than one percent in otherwise healthy individuals steeply rises by up to 30% in these pregnant populations. Answering this pivotal question has not been a simple task. HEV, in general, has been a difficult pathogen to understand in the laboratory setting. A historical lack of ability to efficiently propagate the virus in tissue culture models has led to many molecular aspects of the viral lifecycle being understudied. Although great strides have been made in recent years to adapt viruses to cell culture, this field remains behind other viruses that are much easier to replicate efficiently in vitro. Some of the greatest discoveries regarding HEV have come from using animal models for which naturally occurring strains of HEV have been identified, including pigs and chickens, but key limitations have made animal models imperfect for studying all aspects of human HEV infections. In addition to the difficulties working with HEV, pregnancy is a very complicated biological process with an elaborate interplay between many different host systems, including hormones, cardiovascular, kidneys, respiratory, gastrointestinal, epithelial, liver, metabolic, immune, and others. Significant differences between the timing and interplay of these systems are notable between species, and making direct comparisons between animals and humans can be difficult at times. No simple answer exists as to how HEV enhances mortality in pregnant populations. One of the best approaches to studying HEV in pregnancy is likely a combinatorial approach that uses the best combination of emerging in vitro and in vivo systems while accounting for the deficiencies that are present in each model. This review describes many of the current HEV animal model systems and the strengths and weaknesses of each as they apply to HEV pregnancy-associated mortality. We consider factors that are critical to analyzing HEV infection within the host and how, despite no perfect animal model for human pregnancy mortality existing, recent developments in HEV models, both in vitro and in vivo, are advancing our overall understanding of HEV in the pregnant host.
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12
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Zhao C, Wang Y. Laboratory Diagnosis of HEV Infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:199-213. [PMID: 37223868 DOI: 10.1007/978-981-99-1304-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Serological and nucleic acid tests for detecting hepatitis E virus (HEV) have been developed for both epidemiologic and diagnostic purposes. The laboratory diagnosis of HEV infection depends on the detection of HEV antigen or HEV RNA in the blood, stool, and other body fluids, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies and low avidity IgG can be detected during the acute phase of the illness and can last approximately 12 months, representing primary infection, whereas anti-HEV IgG antibodies can last more than several years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, low avidity IgG, HEV antigen, and HEV RNA, while epidemiological investigations are mainly based on anti-HEV IgG. Although significant progress has been made in developing and optimizing different formats of HEV assays, improving their sensitivity and specificity, there are many shortcomings and challenges in inter-assay concordance, validation, and standardization. This article reviews the current knowledge on the diagnosis of HEV infection, including the most common available laboratory diagnostic techniques.
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Affiliation(s)
- Chenyan Zhao
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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13
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Aziz AB, Øverbø J, Dudman S, Julin CH, Kwon YJG, Jahan Y, Ali M, Dembinski JL. Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh. Viruses 2022; 15:63. [PMID: 36680103 PMCID: PMC9866510 DOI: 10.3390/v15010063] [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: 10/30/2022] [Revised: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV.
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Affiliation(s)
- Asma Binte Aziz
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- International Vaccine Institute (IVI), Seoul 08800, Republic of Korea
| | - Joakim Øverbø
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | - Susanne Dudman
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
| | - Cathinka Halle Julin
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | | | - Yasmin Jahan
- Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0046, Japan
| | - Mohammad Ali
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, MD 21205, USA
| | - Jennifer L. Dembinski
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
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14
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Samala N, Wang RY, Auh S, Balla AK, Dakhoul L, Alter HJ, Farci P, Ghabril M, Lucey MR, Rangnekar AS, Reddy KR, Ghany MG. Hepatitis E prevalence and infection in solid-organ transplant recipients in the United States. J Viral Hepat 2022; 29:1134-1142. [PMID: 36036116 DOI: 10.1111/jvh.13739] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/27/2022] [Accepted: 07/19/2022] [Indexed: 12/29/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ-transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant-recipients, we conducted a prospective, cross-sectional, multicentre study among transplant-recipients and age- and organ-matched waitlist patients. Participants answered a risk-exposure questionnaire and were tested for HEV-RNA (in-house PCR), HEV-IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant-recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p < 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant-recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative-risk of being HEV seropositive increased with older age (RR = 3.4 [1.07-10.74] in patients >70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27-3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03-3.34], p = 0.02); and kidney transplantation (2.4 [1.15-5.16], p = 0.02). HEV-RNA, genotype 3 was detected in only two patients (0.4%), both transplant-recipients. HEV seroprevalence was higher among transplant-recipients than waitlist patients. HEV should be considered in transplant-recipients presenting with graft hepatitis. Detection of HEV-RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant-recipients in the U.S.
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Affiliation(s)
- Niharika Samala
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Richard Y Wang
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Sungyoung Auh
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Abdalla Kara Balla
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Lara Dakhoul
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Harvey J Alter
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Patrizia Farci
- Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Marwan Ghabril
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - K Rajender Reddy
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Marc G Ghany
- Liver Disease Branch (LDB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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15
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Pisano MB, Campbell C, Anugwom C, Ré VE, Debes JD. Hepatitis E virus infection in the United States: Seroprevalence, risk factors and the influence of immunological assays. PLoS One 2022; 17:e0272809. [PMID: 35930611 PMCID: PMC9355204 DOI: 10.1371/journal.pone.0272809] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 07/26/2022] [Indexed: 11/19/2022] Open
Abstract
In the United States (U.S.), a hepatitis E virus (HEV) seroprevalence between 6 and 21% has been described, with a decreasing trend. We aimed to investigate HEV infection in the U.S. population from 2009 to 2016, and examine the differences in seroprevalence using different assays. We used data from the National Health and Nutrition Examination Survey (NHANES-CDC) to estimate HEV seroprevalence and analyze demographic variables related to the infection. Additionally, we compared 4 serological tests used. The estimated HEV seroprevalence between 2009-2016 was 6.1% (95% CI: 5.6%-7.0%) for IgG and 1.02% (0.8%-1.2%) for IgM. Higher HEV IgG prevalences were found in older people, females, non-Hispanic Asians and those born outside of the U.S. The in-house immunoassay and the Wantai HEV-IgG ELISA presented the highest sensitivity values in the tested population. The highest specificity values corresponded to the DSI-EIA-ANTI-HEV-IgG assay. The kappa statistical values showed concordances no greater than 0.64 between the assays. HEV prevalence in our study was similar to previously reported, and a decline in the prevalence was observed through the NHANES assessments (from 1988 to 2016). The sensitivity and specificity of the assays varied widely, making comparisons difficult and highlighting the need to develop a gold standard assay.
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Affiliation(s)
- María Belén Pisano
- Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, CONICET, Córdoba, Argentina
| | - Christopher Campbell
- Cancer Control Section, Minnesota Department of Health, St. Paul, MN, United States of America
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, United States of America
| | - Chimaobi Anugwom
- Department of Medicine, Division of Infectious Diseases and International Medicine and Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN, United States of America
| | - Viviana Elizabeth Ré
- Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, CONICET, Córdoba, Argentina
| | - José D. Debes
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, United States of America
- Department of Medicine, Division of Infectious Diseases and International Medicine and Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN, United States of America
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16
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Fernández Villalobos NV, Kessel B, Rodiah I, Ott JJ, Lange B, Krause G. Seroprevalence of hepatitis E virus infection in the Americas: Estimates from a systematic review and meta-analysis. PLoS One 2022; 17:e0269253. [PMID: 35648773 PMCID: PMC9159553 DOI: 10.1371/journal.pone.0269253] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022] Open
Abstract
Background
Hepatitis E virus (HEV) infection is responsible for inflammatory liver disease and can cause severe health problems. Because the seroprevalence of HEV varies within different population groups and between regions of the continent, we conducted a systematic review on the topic in order to provide evidence for targeted prevention strategies.
Methods
We performed a systematic review in PubMed, SCIELO, LILACS, EBSCO, and Cochrane Library and included reports up to 25 May 2021 (PROSPERO registration number: CRD42020173934). We assessed the risk of bias, publication bias, and heterogeneity between studies and conducted a random-effect meta-analysis for proportions using a (binomial-normal) generalized linear mixed model (GLMM) fitted by Maximum Likelihood (ML). We also reported other characteristics like genotype and risk factors.
Results
Of 1212 identified records, 142 fulfilled the inclusion criteria and were included in the qualitative analysis and 132 in the quantitative analysis. Our random-effects GLMM pooled overall estimate for past infection (IgG) was 7.7% (95% CI 6.4%–9.2%) with high heterogeneity (I2 = 97%). We found higher seroprevalence in certain population groups, for example in people with pig related exposure for IgG (ranges from 6.2%–28% and pooled estimate of 13.8%, 95% CI: 7.6%–23.6%), or with diagnosed or suspected acute viral hepatitis for IgM (ranges from 0.3%–23.9% and pooled estimate of 5.5%, 95% CI: 2.0%–14.1%). Increasing age, contact with pigs and meat products, and low socioeconomic conditions are the main risk factors for HEV infection. Genotype 1 and 3 were documented across the region.
Conclusion
HEV seroprevalence estimates demonstrated high variability within the Americas. There are population groups with higher seroprevalence and reported risk factors for HEV infection that need to be prioritized for further research. Due to human transmission and zoonotic infections in the region, preventive strategies should include water sanitation, occupational health, and food safety.
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Affiliation(s)
| | - Barbora Kessel
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Isti Rodiah
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Jördis Jennifer Ott
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
- Hannover Medical School, Hannover, Germany
| | - Berit Lange
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
- German Centre for Infection Research (DZIF), Braunschweig, Germany
| | - Gérard Krause
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
- Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), Braunschweig, Germany
- Twincore, Centre for Experimental and Clinical Infection Research, Braunschweig-Hannover, Germany
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17
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Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems. Cells 2022; 11:cells11060927. [PMID: 35326378 PMCID: PMC8946046 DOI: 10.3390/cells11060927] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 12/04/2022] Open
Abstract
Background: Hepatitis C virus (HCV) constitutes a global health problem, while hepatitis E virus (HEV) is the major cause of acute viral hepatitis globally. HCV/HEV co-infections have been poorly characterized, as they are hampered by the lack of robust HEV cell culture systems. This study developed experimental models to study HCV/HEV co-infections and investigate viral interference in cells and humanized mice. Methods: We used state-of-the art human hepatocytes tissue culture models to assess HEV and HCV replication in co- or super-transfection settings. Findings were confirmed by co- and super-infection experiments in human hepatocytes and in vivo in human liver chimeric mice. Results: HEV was inhibited by concurrent HCV replication in human hepatocytes. This exclusion phenotype was linked to the protease activity of HCV. These findings were corroborated by the fact that in HEV on HCV super-infected mice, HEV viral loads were reduced in individual mice. Similarly, HCV on HEV super-infected mice showed reduced HCV viral loads. Conclusion: Direct interference of both viruses with HCV NS3/4A as the determinant was observed. In vivo, we detected reduced replication of both viruses after super-infection in individual mice. These findings provide new insights into the pathogenesis of HCV-HEV co-infections and should contribute to its clinical management in the future.
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18
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Bagulo H, Majekodunmi AO, Welburn SC, Bimi L. Hepatitis E seroprevalence and risk factors in humans and pig in Ghana. BMC Infect Dis 2022; 22:132. [PMID: 35130864 PMCID: PMC8822658 DOI: 10.1186/s12879-022-07127-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/31/2022] [Indexed: 11/10/2022] Open
Abstract
Background Although Hepatitis E virus (HEV) infection has significant negative impact on the health and wellbeing of underprivileged populations, the burden of HEV in Ghana is still unclear, despite widespread water, sanitation, and hygiene (WASH) related conditions that predispose people to the risk of infection. Methods A cross-sectional study was conducted to explore rates of HEV seroprevalence and HEV prevalence, as well as risk factors in humans and domestic pigs in Ghana. These were determined using ELISAs manufactured by Wantai Beijing Biopharmaceuticals, China. The study involved 1365 community members, 105 pig farmers and 474 domestic pigs from four administrative regions of Ghana. Results Results showed overall seroprevalence and prevalence of 12.4% and 0.7% in community members and 15.2% and 2.9% in pig farmers respectively. There was no significant difference in the seroprevalence between the two groups (Z = 0.851; p = 0.3953). However, the prevalence in pig farmers was significantly higher than in community members (Z = 2.412; p = 0.016). Age (OR = 1.369, CI = 1.243 – 1.508; p = 0.0000), gender (OR = 1.419, CI = 1.101 – 1.991; p = 0.043), and the region of residence (OR = 1.569, CI = 1.348 – 1.827; p = 0.0000) were significant risk factors for HEV seroprevalence in a multivariate regression model. In pigs, overall seroprevalence and prevalence of 62.4% and 5.5% were recorded respectively. A significant difference in seroprevalence was found between confined (6.7%) and free-range pigs (88.3%), (Z = 7.492; p < 0.00001) in the Volta Region. Multivariate logistic regression showed a significant association between seroprevalence and husbandry (OR = 7.051, CI = 3.558– 13.972; p = 0.0000) and region (OR = 4.602, CI = 2.300 – 9.205; p = 0.0000) in pigs in the Volta and Greater Accra Region. Conclusion From this study, HEV is endemic in Ghana with high seroprevalence in humans and pig populations. This underscores the need for awareness creation and action for prevention and control.
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Affiliation(s)
- Husein Bagulo
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang, 314400, People's Republic of China. .,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, Legon, P. O Box LG 38, Accra, Ghana. .,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.
| | - Ayodele O Majekodunmi
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang, 314400, People's Republic of China.,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, Legon, P. O Box LG 38, Accra, Ghana.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK
| | - Susan C Welburn
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang, 314400, People's Republic of China.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK
| | - Langbong Bimi
- Department of Animal Biology & Conservation Science, College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana
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19
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Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
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Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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20
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Trongtorsak A, Chaisidhivej N, Yadav K, Kim J, Thongprayoon C, Cheungpasitporn W, Hansrivijit P. Hepatitis E virus infection in hematopoietic stem cell transplant recipients: a systematic review and meta-analysis. J Investig Med 2021; 70:853-858. [PMID: 34930797 DOI: 10.1136/jim-2021-002102] [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] [Accepted: 11/05/2021] [Indexed: 01/30/2023]
Abstract
Although most patients with hepatitis E virus (HEV) infection are asymptomatic or have mild symptoms, its infection is generally underdiagnosed and overlooked. In immunocompromised patients, HEV infection can lead to acute liver failure and death. However, the clinical evidence of HEV infection in hematopoietic stem cell transplant (HSCT) recipients is scarce; thus, we conducted this systematic review and meta-analysis to assess the prevalence of HEV infection in this population. We searched MEDLINE, EMBASE, and the Cochrane Library databases from inception through October 2020 to identify studies that reported the prevalence of HEV infection among HSCT recipients. HEV infections were confirmed by HEV-IgG/IgM or HEV-RNA assay. A total of 1977 patients from nine studies with a follow-up time up to 40 months were included in the final analysis. The pooled prevalence of positive HEV-RNA was 3.0% (95% CI 2.3% to 4.0%). The pooled prevalence of positive HEV-IgG was 10.3% (95% CI 4.5% to 21.8%). The pooled prevalence of de novo HEV infection was 2.9% (95% CI 1.8% to 4.5%). Age and male gender were not associated with HEV-RNA or HEV-IgG positivity in the meta-regression analysis. In conclusion, the prevalence of HEV-IgG in HSCT recipients was about 10%, while the prevalence of HEV-RNA was only 3%. However, further studies that focus on the clinical outcomes in this population are warranted.
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Affiliation(s)
- Angkawipa Trongtorsak
- Department of Internal Medicine, Amita Health Saint Francis Hospital, Evanston, Illinois, USA
| | - Natapat Chaisidhivej
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA
| | - Kritika Yadav
- Department of Internal Medicine, Amita Health Saint Francis Hospital, Evanston, Illinois, USA
| | - Jinah Kim
- Department of Internal Medicine, UPMC Pinnacle Harrisburg, Harrisburg, Pennsylvania, USA
| | | | | | - Panupong Hansrivijit
- Department of Internal Medicine, UPMC Pinnacle Harrisburg, Harrisburg, Pennsylvania, USA
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21
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Wong RJ, Cheung R, Gish RG, Chitnis AS. Prevalence of hepatitis E infection among adults with concurrent chronic liver disease. J Viral Hepat 2021; 28:1643-1655. [PMID: 34415657 DOI: 10.1111/jvh.13597] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 01/17/2023]
Abstract
While hepatitis E virus (HEV) infection can increase the risk of liver decompensation and death in patients with underlying chronic liver disease (CLD), prevalence of HEV in this cohort is not well reported. Using data from the 2011-2018 National Health and Nutrition Examination Survey, we aim to evaluate seroprevalence of HEV IgG among adults with non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV). HEV IgG seroprevalence between groups was evaluated with chi-square testing, and adjusted multivariate logistic regression models evaluated for predictors of seropositivity for HEV IgG. Seroprevalence of HEV IgG was 6.58% in ALD, 8.66% in HCV, 8.81% in NAFLD and 19.86% in HBV. We observed increasing HEV IgG seroprevalence over time in our study period, and in 2015-2018, seroprevalence was highest among the individuals with HCV (10.00%) and HBV (30.30%). Older age and being born outside of the United States were associated with seropositivity for HEV IgG in ALD, NAFLD, HBV, and for HCV, older age and being at or below poverty level were associated with seroprevalence for HEV IgG. In conclusion, we observed a relatively high prevalence of HEV among adults with CLD. These data highlight the need for greater awareness and education about the role of HEV in patients with underlying CLD, improving HEV test diagnostics, and revisiting the discussion about the potential role of HEV vaccines in CLD patients who are at higher risk of decompensation and death from acute HEV infection.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.,Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.,Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Robert G Gish
- Hepatitis B Foundation, Doylestown, Pennsylvania, USA
| | - Amit S Chitnis
- Tuberculosis Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, California, USA
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22
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Mrzljak A, Balen I, Barbic L, Ilic M, Vilibic-Cavlek T. Hepatitis E virus in professionally exposed: A reason for concern? World J Hepatol 2021; 13:723-730. [PMID: 34367494 PMCID: PMC8326162 DOI: 10.4254/wjh.v13.i7.723] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 03/31/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
The zoonotic risk of hepatitis E virus (HEV) is well established. The HEV seroprevalence rates vary according to geographical region, assays used, and study cohorts. HEV infection is still underdiagnosed, implying the need to evaluate the disease's burden in the general population and specific risk groups, such as professionally exposed. Close contact with various animal reservoirs such as pigs, rabbits, sheep, dogs, wild boars, and deer has been associated with higher anti-HEV seroprevalence as a part of occupational exposure. While exact transmission routes remain to be determined, some general preventive measures such as proper hand hygiene, the usage of personal protective equipment, and the thermal processing of food before consumption should be followed. A "One-Health" multisectoral approach should be implemented to achieve optimal health and well-being outcomes, recognizing the interconnections between humans, animals, plants, and their shared environment, in which a vaccine against the zoonotic genotypes 3 and 4 and swine vaccination should be considered as a possible public health measure. This opinion review comprehensively addresses the HEV burden of professional exposure for butchers, slaughterhouse workers, veterinarians, farmers, hunters, and forestry workers delineates the current limits of protective work measures, and tackles future directions.
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Affiliation(s)
- Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Virology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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23
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Sherman KE, Kottilil S, Rouster SD, Abdel-hameed EA, Boyce CL, Meeds HL, Terrault N, Shata MT. Hepatitis E Infection in a Longitudinal Cohort of Hepatitis C Virus and HCV/HIV Coinfected Persons. AIDS Res Hum Retroviruses 2021; 37:534-541. [PMID: 33794657 DOI: 10.1089/aid.2020.0303] [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] [Indexed: 12/24/2022] Open
Abstract
Hepatitis E virus (HEV) is thought to be common in the United States with increased prevalence in those with concomitant hepatitis C virus (HCV) or HCV/HIV coinfection. Little is known regarding true prevalence, incidence, and antibody seroreversion in these populations. We sought to define these rates among HCV and HCV/HIV coinfected persons in the Washington, DC area. Two longitudinal cohorts of HCV and HCV/HIV coinfected subjects from the Washington, DC area were evaluated. Multiple HEV test modalities were deployed including immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody testing, evaluation of antibody avidity, HEV RNA testing, and HEV enzyme-linked immune absorbent spot (ELISPOT) analysis. A total of 379 individuals were evaluated including 196 who were HCV monoinfected and 183 HCV/HIV coinfected. Anti-HEV IgG was detected and confirmed in 18.7% of the cohort at baseline. None demonstrated anti-HEV IgM positive or HEV RNA positive results. Proportions of HEV antibody prevalence did not significantly differ between groups. Longitudinal follow-up samples were available for 226 individuals with a mean follow-up time of 24 months. Seroreversion was noted in 1.8%. One HCV/HIV infected person seroconverted to HEV IgG positivity in the followed cohort. About 40% of the positive population demonstrated high avidity suggestive of more remote exposure. Interferon gamma ELISPOT was performed in 70 subjects and false negative and false positive HEV enzyme-linked immunosorbent assay antibodies were identified. In HIV-infected persons in the United States HEV exposure and seroconversion is frequent enough that HEV should be considered in the differential diagnosis of acute hepatitis. Seroreversion may lead to underestimation of true infection risk.
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Affiliation(s)
- Kenneth E Sherman
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, College of Medicine Digestive Diseases, 231 Albert Sabin Way, Cincinnati, Ohio, United States, 45267
- University of Cincinnati
| | - Shyam Kottilil
- University of Maryland Baltimore, 12265, Institute of Human Virology, Baltimore, Maryland, United States
| | - Susan D Rouster
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, Cincinnati, Ohio, United States
| | - Enass A. Abdel-hameed
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, Cincinnati, Ohio, United States
| | - Ceejay L. Boyce
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, Cincinnati, Ohio, United States
| | - Heidi L Meeds
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, Cincinnati, Ohio, United States
| | - Norah Terrault
- University of Southern California Keck School of Medicine, 12223, Division of GI and Liver, Los Angeles, California, United States
| | - M. Tarek Shata
- University of Cincinnati College of Medicine, 12303, Internal Medicine Digestive Diseases, Cincinnati, Ohio, United States
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24
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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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25
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Wasuwanich P, Ingviya T, Thawillarp S, Teshale EH, Kamili S, Crino JP, Scheimann AO, Argani C, Karnsakul W. Hepatitis E-Associated Hospitalizations in the United States: 2010-2015 and 2015-2017. J Viral Hepat 2021; 28:672-681. [PMID: 33306246 DOI: 10.1111/jvh.13458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/13/2020] [Accepted: 11/18/2020] [Indexed: 12/19/2022]
Abstract
Hepatitis E is considered rare in the United States (US) despite its widespread occurrence in Asian and African countries. The objective of this study was to describe the characteristics of hepatitis E-related pregnancies and acute-on-chronic liver failure and analyse trends for hepatitis E diagnosis among hospitalized patients in the US. We examined data from the 2010-2017 National Inpatient Sample from Healthcare Cost and Utilization Project to determine mortality, morbidity, pregnancy diagnoses, chronic liver disease diagnoses, and other conditions during hospitalization. Data were extracted for hospitalizations with hepatitis E as defined by ICD-9 codes 070.43 and 070.53 and ICD-10 code B17.2. Of 208,462,242 hospitalizations from 2010-2015, we identified 960 hepatitis E hospitalizations. The hospitalization rate of hepatitis E was 3.7 per 10 million in 2010 and 6.4 per 10 million in 2015 (β = 0.60, p = 0.011). From 2015 to 2017, the hospitalization appeared to increase with slope (β) of 0.50. Among those hospitalizations, 34 (4%) died and 85 (9%) had acute-on-chronic liver failure. Ninety-five (10%) had a diagnosis of pregnancy, there were no reports of maternal or foetus/neonate deaths, but there was a high proportion of adverse events for both during hospitalization. Having a chronic liver disease was associated with hepatic coma diagnosis (OR = 10.94, p = 0.002). Although the hospitalization rate of hepatitis E in the US is low, it appears to be increasing over time. Further studies are necessary in order to conclude a causal association of hepatitis E with adverse events and mortalities in pregnancy and chronic liver disease in the US.
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Affiliation(s)
- Paul Wasuwanich
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA
| | - Thammasin Ingviya
- Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA.,Department of Family and Preventive Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Supharerk Thawillarp
- Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Eyasu H Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, GA, USA
| | - Saleem Kamili
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, GA, USA
| | - Jude P Crino
- Department of Gynecology and Obstetrics, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Ann O Scheimann
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cynthia Argani
- Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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26
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Obeidat AE, Monti G, Sae-Ow W, Shinoda H, Lim H. Hepatitis E Virus Superinfection: an Underrecognized Trigger of Acute Hepatitis B Virus Flare. Cureus 2021; 13:e13809. [PMID: 33859880 PMCID: PMC8038892 DOI: 10.7759/cureus.13809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a significant cause of acute hepatitis in endemic areas, such as parts of Asia, Africa, and Mexico, though HEV prevalence in the United States has been estimated between 6% and 20%. Chronic hepatitis B virus (HBV) infection affects about 1 per 1.4 million people in North America. Although well documented in Asia, HBV flare secondary to HEV superinfection is rarely reported in the United States. Here, we present a case of chronic undiagnosed HBV infection with acute flare secondary to HEV superinfection.
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Affiliation(s)
| | - Gabriel Monti
- School of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, USA
| | - Wichit Sae-Ow
- Pathology, The Queen's Medical Center, Honolulu, USA
| | | | - Herbert Lim
- Gastroenterology and Hepatology, The Queen's Medical Center, Honolulu, USA
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27
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Kmush BL, Lu AM, Spillane T, Hruska B, Gump BB, Bendinskas KG. Seroprevalence of hepatitis E virus antibodies in adults and children from upstate New York: A cross-sectional study. PLoS One 2021; 16:e0245850. [PMID: 33497387 PMCID: PMC7837474 DOI: 10.1371/journal.pone.0245850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 01/10/2021] [Indexed: 11/19/2022] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis around the world, especially in developing countries. Recently, HEV has also been recognized as important cause of hepatitis in Europe and Japan, however, there is a paucity of clinical data from the United States. The overall seroprevalence of HEV antibodies is around 10% in the United States, but considerable variation is seen based on geographic location, year, and assay used. In this study, 63 adults and 417 children from New York State were tested for anti-HEV IgG antibodies using the commercially available Wantai IgG assay. The overall seroprevalence of HEV antibodies among adult participants was 9.52% (95% CI: 3.58–19.59%). Positive adults tended to be older than HEV negative adults, all positive adults were female. Only 3 (0.7%, 95% CI:: 0.15–2.09%) of the children were positive, all positive children were male. These results are consistent with global and United States trends in HEV seroprevalence.
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Affiliation(s)
- Brittany L. Kmush
- Department of Public Health, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States of America
- * E-mail:
| | - Amelia M. Lu
- Department of Public Health, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States of America
| | - Taylor Spillane
- Department of Public Health, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States of America
| | - Bryce Hruska
- Department of Public Health, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States of America
| | - Brooks B. Gump
- Department of Public Health, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States of America
| | - Kestutis G. Bendinskas
- Department of Chemistry, State University of New York, Oswego, New York, United States of America
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28
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Fontana RJ, Engle RE, Gottfried M, Hammed B, Hanje J, Durkalski V, Kleiner DE, Nguyen H, Nishimura N, Lee WM, Farci P. Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury. Clin Transl Gastroenterol 2020; 11:e00273. [PMID: 33259165 PMCID: PMC7665257 DOI: 10.14309/ctg.0000000000000273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/07/2020] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E. Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Michelle Gottfried
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Bilal Hammed
- Department of Medicine, UCSF, San Francisco, California, USA
| | - James Hanje
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hanh Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Norihisa Nishimura
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - William M. Lee
- Department of Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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29
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Zhang Q, Zong X, Li D, Lin J, Li L. Performance Evaluation of Different Commercial Serological Kits for Diagnosis of Acute Hepatitis E Viral Infection. Pol J Microbiol 2020; 69:217-222. [PMID: 32548990 PMCID: PMC7324857 DOI: 10.33073/pjm-2020-025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 05/04/2020] [Accepted: 05/09/2020] [Indexed: 12/24/2022] Open
Abstract
Clinical diagnosis of hepatitis E viral (HEV) infection mainly relies on serological assays, and the current status of misdiagnoses regarding HEV infection is uncertain. In this study, patients with acute HEV infection were tested for anti-HEV IgM and IgG, a HEV antigen (Ag), and viral loads (HEV RNA). Serology was performed using four commercial HEV ELISA kits: Wantai, Kehua, Lizhu, and Genelabs IgM and IgG. The HEV RNA was detected using RT-PCR assays. The sensitivities of different kits for anti-HEV IgM ranged from 82.6% to 86%. Each kit for anti-HEV IgM was highly specific (97.8–100%). The sensitivities of all kits to detect anti-HEV IgG with (87.2–91.9%) had a substantial agreement, but the Kehua and Genelabs tests were more specific than the Wantai and Lizhu tests. The Wantai tests for the HEV Ag and HEV RNA were also important for acute HEV infections (Kappa = 0.787). Furthermore, a total of 6.98% of HEV infections were positive for HEV RNA but negative for both the HEV Ag and anti-HEV antibodies of IgM and IgG classes. Our findings demonstrate that the diagnosis of hepatitis E may be missed if only serological assays are used. Thus, a combination of serological and nucleic acid testing provides the optimal sensitivity and specificity to the diagnostic process.
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Affiliation(s)
- Qiang Zhang
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
| | - Xiaolong Zong
- Department of Clinical Laboratory , The Second Hospital of Tianjin Medical University , Tianjin , China
| | - Dongming Li
- Department of Clinical Laboratory , Tianjin Third Central Hospital , Tianjin , China
| | - Jing Lin
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
| | - Lihua Li
- Department of Clinical Laboratory , Branch of Tianjin Third Central Hospital , Tianjin , China
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30
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Wilhelm B, Waddell L, Greig J, Young I. A systematic review and meta-analysis of predictors of human hepatitis E virus exposure in non-endemic countries. Zoonoses Public Health 2020; 67:391-406. [PMID: 32196945 PMCID: PMC7317350 DOI: 10.1111/zph.12698] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/19/2019] [Accepted: 02/04/2020] [Indexed: 12/15/2022]
Abstract
The reported incidence of clinical hepatitis E cases is rising in some non-endemic countries, with concurrent concerns regarding potential hepatitis E virus (HEV) contamination of the blood supply. Therefore, the characterization of major potential sources of human HEV exposure is important to inform risk assessment and public health policy. A systematic review was conducted, including a comprehensive search in six electronic bibliographic databases, verified by hand-searching reference lists of HEV reviews, and a grey literature search, of the broad research question 'what is the evidence of the association between predictors of human HEV exposure, and HEV IgG seropositivity, in non-endemic countries?' Using forms designed a priori, captured studies were appraised at first-level screening, second-level characterization, and third-level data extraction and risk of bias assessment. Meta-analysis yielded summary estimates of association between potential predictors and odds of HEV seropositivity. Meta-analysis and meta-regression of the odds of HEV seroprevalence in specific groups characterized potential sources of HEV exposure. From 4,163 captured citations, 245 relevant studies underwent data extraction, investigating HEV seroprevalence or predictors in both healthy subjects and targeted patient groups. Across these groups, increasing age was a predictor of HEV IgG seropositivity. Both human immunodeficiency virus patients and haemodialysis patients had significantly increased odds of HEV seropositivity relative to the general population. Working with pigs, in forestry, or in hospitals, was significantly associated with increased odds of HEV seropositivity, as were consumption of meat, pork or game meat, or hunting. Chronological time was not associated with HEV seropositivity within our data sets. Further study of the distribution of potential dietary or behavioural predictors between high and lower prevalence areas within non-endemic countries could improve our understanding of the relative importance of specific HEV transmission pathways.
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Affiliation(s)
| | - Lisa Waddell
- Public Health Risk Sciences DivisionNational Microbiology LaboratoryPublic Health Agency of CanadaGuelphONCanada
| | - Judy Greig
- Public Health Risk Sciences DivisionNational Microbiology LaboratoryPublic Health Agency of CanadaGuelphONCanada
| | - Ian Young
- School of Occupational and Public HealthRyerson UniversityTorontoONCanada
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31
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Whitsett M, Feldman DM, Jacobson I. Hepatitis E Virus Infection in the United States: Current Understanding of the Prevalence and Significance in the Liver Transplant Patient Population and Proposed Diagnostic and Treatment Strategies. Liver Transpl 2020; 26:709-717. [PMID: 32061053 DOI: 10.1002/lt.25732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 01/28/2020] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV), of the family Herpesviridae, is a virus that infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus that afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population because of its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.
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Affiliation(s)
- Maureen Whitsett
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - David M Feldman
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - Ira Jacobson
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
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Abi Nader E, Girard M, Leruez-Ville M, Sissaoui S, Lacaille F, Roque-Afonso AM, Debray D. Seroprevalence of Hepatitis E virus infection in children after liver transplantation: A single-center experience in France. Clin Res Hepatol Gastroenterol 2020; 44:174-180. [PMID: 31266724 DOI: 10.1016/j.clinre.2019.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 05/26/2019] [Accepted: 06/05/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide, usually asymptomatic in children. However, a growing number of publications over the last decade have documented cases of chronic hepatitis related to HEV-genotype 3 infection, and progressing to cirrhosis in immuno-compromised patients, particularly in adult kidney transplant recipients. The aim of our study was to evaluate the prevalence and severity of HEV infection among pediatric liver transplant (PLT) recipients managed in our center. MATERIAL AND METHODS Between November 1st 2014 and January 1st 2016, PLT recipients (less than 18 years-old) were screened for HEV infection [determined by HEV serology, HEV- immunoglobulin M (IgM) and immunoglobulin G (IgG), and HEV-ribonucleic acid (RNA) by reverse transcriptase polymerase chain reaction] at their annual follow-up visit. RESULTS Eighty children were tested for HEV infection a mean of 5.4±5.3 years after liver transplantation (LT). The main indication for LT was biliary atresia (n=47, 59%). The prevalence of HEV-IgG was 8% (n=6; age range 1.3 to 14.2 years-old at the time of HEV testing). Prevalence increased to 30% when considering only the 20 children with a past history of an unexplained episode of elevated transaminases since LT. None had HEV IgM, serum HEV-RNA, or increased transaminases at the time of HEV testing. Among the six IgG seropositive children, two had received intravenous immunoglobulins prior to screening and four children had a negative control (seroreversion) 3 to 42 months after the first testing. CONCLUSION The prevalence of HEV infection in our cohort is low and similar to other pediatric reports. We saw no cases of chronic hepatitis or fibrosis attributable to HEV. The lower immunosuppressive regimen used in PLT children compared to other solid organ transplant recipients may account for this good outcome.
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Affiliation(s)
- Elie Abi Nader
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France; University of Paris-Descartes, Sorbonne Paris-Cité, 75006 Paris, France.
| | - Muriel Girard
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France; University of Paris-Descartes, Sorbonne Paris-Cité, 75006 Paris, France
| | - Marianne Leruez-Ville
- Department of Virology, Necker-Enfants-Malades University Hospital, AP-HP, 75015 Paris, France
| | - Samira Sissaoui
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France
| | - Florence Lacaille
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France
| | - Anne-Marie Roque-Afonso
- Inserm U1993, Department of Virology, National Reference Center for Hepatitis A and Hepatitis E, Paul-Brousse Hospital, AP-HP, 94800 Villejuif, France; University of Paris-Sud, 91405 Paris, France
| | - Dominique Debray
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France; University of Paris-Descartes, Sorbonne Paris-Cité, 75006 Paris, France
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Amoroso P, Buonocore S, Lettieri G, Pesce G, Pierri P, De Sena R, Morelli G, Matteis B, Dell'isola C, De Marino V, Ciccaglione AR, Punzi R, Esposito C, Spada E. Changing epidemiology of acute liver failure in Italy: a single-center experience over 25 years. Minerva Med 2020; 111:330-336. [PMID: 31958920 DOI: 10.23736/s0026-4806.19.06331-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Acute liver failure (ALF) is a rare but often lethal syndrome. In Italy, recent data on its incidence and causes are lacking. We report here the epidemiological analysis of ALF cases observed in Campania, a Southern Italian region, over the last 25 years. METHODS Medical records of ALF cases hospitalized from 1992 to 2018 were retrospectively analyzed. RESULTS Two hundred ten ALF cases occurred during 1992-2018: 103 (49%) hepatitis B virus (HBV)-related (including 5 cases also infected with Delta virus), 39 (19%) from undetermined cause, 36 (17%) drug-induced, 11 (5%) Wilson's disease-associated, 8 (4%) hepatitis A virus (HAV)-related and 12 (6%) from other causes. Separate time-periods analysis of data showed a significant progressive decrease in ALF incidence mainly attributable to a decline of HBV and other viruses etiology. Already before 2010, HAV or Delta virus-related cases have no longer been observed. No hepatitis C or E virus-related ALF was detected through the study period. A progressive decrease in frequency of ALF due to undetermined causes or drug was also evident. CONCLUSIONS A decrease in ALF incidence and a changing in its etiology were observed in Campania during 1992-2018. Both results were likely mainly due to 1991 introduction of HBV universal vaccination and may be considered generalizable nationwide.
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Affiliation(s)
- Pietro Amoroso
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy -
| | | | - Gennaro Lettieri
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Gaetano Pesce
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Paola Pierri
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Raffaele De Sena
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Giuseppe Morelli
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Bianca Matteis
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Chiara Dell'isola
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Valeria De Marino
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Anna R Ciccaglione
- Department of Infectious Diseases, National Institute of Health, Rome, Italy
| | - Rodolfo Punzi
- Department of Infectious Diseases, D. Cotugno Hospital, Naples, Italy
| | - Ciro Esposito
- Department of Transplants, A. Cardarelli Hospital, Naples, Italy
| | - Enea Spada
- Department of Infectious Diseases, National Institute of Health, Rome, Italy
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Chauhan A, Webb G, Ferguson J. Clinical presentations of Hepatitis E: A clinical review with representative case histories. Clin Res Hepatol Gastroenterol 2019; 43:649-657. [PMID: 30808575 PMCID: PMC6864596 DOI: 10.1016/j.clinre.2019.01.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 01/03/2019] [Accepted: 01/21/2019] [Indexed: 02/04/2023]
Abstract
Hepatitis E virus (HEV) typically causes an acute, self-limiting hepatitis and is among the commonest cause of such presentations. Hepatitis E viral infection is also increasingly recognized as a cause of chronic hepatitis amongst the immunocompromised, particularly amongst solid organ transplant recipients. Chronic HEV infection remains an underdiagnosed disease and chronic infection can lead to rapidly progressive liver fibrosis and cirrhosis. This review examines current understanding of the HEV. We illustrate typical clinical presentations, management strategies [(based upon guidelines from both the British Transplant Society (BTS) and European Association for the study of liver (EASL)] and outcomes of HEV infection in different cohorts of patients by highlighting select transplant and non-transplant patient cases, from one of the largest tertiary Hepatology centres in Europe.
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Affiliation(s)
- Abhishek Chauhan
- NIHR Birmingham Biomedical Research Centre, United Kingdom; Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom.
| | - Gwilym Webb
- Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
| | - James Ferguson
- Liver unit, University Hospitals Birmingham, United Kingdom
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Abstract
Notified cases of hepatitis E have increased 40-fold in the past 10 years in Germany. Food safety is a major concern as hepatitis E virus (HEV) RNA has been detected in ready-to-eat retail-level food products. The objective of this case–control study was to assess risk factors for autochthonous symptomatic hepatitis E and explore reasons for delays in diagnosis. Methods: Demographic, clinical and exposure data from notified hepatitis E cases and individually matched population controls were collected in semi-standardised telephone interviews. Conditional logistic regression analysis was used to calculate matched odds ratios (mOR) and population attributable fractions (PAF). Results: In total, 270 cases and 1,159 controls were included (mean age 53 years, 61% men in both groups). Associated with disease were: consumption of undercooked pork liver, pork, wild boar meat, frankfurters, liver sausage and raw vegetables; contact with waste water (occupational) and various host factors (mORs between 1.9 and 34.1, p value < 0.03). PAF for frankfurters and liver sausage were 17.6%, and 23.6%, respectively. There were statistically significant differences in the clinical presentation and hospitalisation proportion of acute hepatitis E in men and women. Diagnosis was preceded by more invasive procedures in 29.2% of patients, suggesting that hepatitis E was not immediately considered as a common differential diagnosis. Conclusions: Our study suggests that there are indeed sex-specific differences in disease development and lends important epidemiological evidence to specific ready-to-eat pork products as a major source for autochthonous hepatitis E. A review of existing consumer recommendations and production methods may be indicated.
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Affiliation(s)
- Mirko Faber
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Mona Askar
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Klaus Stark
- Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
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36
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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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37
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Nelson KE, Labrique AB, Kmush BL. Epidemiology of Genotype 1 and 2 Hepatitis E Virus Infections. Cold Spring Harb Perspect Med 2019; 9:a031732. [PMID: 29735579 PMCID: PMC6546036 DOI: 10.1101/cshperspect.a031732] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Hepatitis E virus (HEV) genotypes 1 and 2 are responsible for the majority of acute viral hepatitis infections in endemic areas in South Asia and sub-Saharan Africa. In addition to frequent sporadic illnesses throughout the year, these viruses often cause large epidemics in association with monsoon rains in Asia or during humanitarian crises in Africa. Clinical hepatitis commonly involves adults more often than young children, with an overall mortality of ∼1%. However, the mortality among pregnant women is often 30% or higher. HEV infection in pregnant women frequently leads to infant mortality or premature delivery. Hepatitis E is an important, yet largely neglected, global public health problem.
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Affiliation(s)
- Kenrad E Nelson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205
| | - Alain B Labrique
- Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205
| | - Brittany L Kmush
- Department of Public Health, Food Studies, and Nutrition, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York 13244
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38
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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39
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Boon D, Redd AD, Laeyendecker O, Engle RE, Nguyen H, Ocama P, Boaz I, Ndyanabo A, Kiggundu V, Reynolds SJ, Gray RH, Wawer MJ, Purcell RH, Kirk GD, Quinn TC, Stabinski L. Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the Rakai District, Uganda. J Infect Dis 2019; 217:785-789. [PMID: 29186448 DOI: 10.1093/infdis/jix610] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 11/22/2017] [Indexed: 11/14/2022] Open
Abstract
A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)-infected adults frequency matched on age, sex, and community to 500 HIV-uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1 HIV-infected individual was actively infected with a genotype 3 virus. Using modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95% confidence interval [CI], 1.071-1.450) and chronic hepatitis B virus infection (PR = 1.377; 95% CI, 1.090-1.738) were associated with HEV seroprevalence. HIV infection status (PR = 0.973; 95% CI, 0.852-1.111) was not associated with HEV seroprevalence. These data suggest there is a large burden of prior exposure to HEV in rural Uganda.
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Affiliation(s)
- Denali Boon
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.,Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Andrew D Redd
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.,Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Oliver Laeyendecker
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.,Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Ronald E Engle
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Hanh Nguyen
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Ponsiano Ocama
- Department of Medicine Makerere University, Kampala, Uganda
| | - Iga Boaz
- Rakai Health Sciences Program, Entebbe, Uganda
| | | | | | - Steven J Reynolds
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.,Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Ronald H Gray
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Rakai Health Sciences Program, Entebbe, Uganda
| | - Maria J Wawer
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Rakai Health Sciences Program, Entebbe, Uganda
| | - Robert H Purcell
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Gregory D Kirk
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Thomas C Quinn
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Lara Stabinski
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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McGivern DR, Lin HHS, Wang J, Benzine T, Janssen HLA, Khalili M, Lisker-Melman M, Fontana RJ, Belle SH, Fried MW. Prevalence and Impact of Hepatitis E Virus Infection Among Persons With Chronic Hepatitis B Living in the US and Canada. Open Forum Infect Dis 2019; 6:ofz175. [PMID: 31139669 DOI: 10.1093/ofid/ofz175] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 04/05/2019] [Indexed: 01/02/2023] Open
Abstract
Background Patients with chronic hepatitis B virus (HBV) may experience spontaneous biochemical flares of liver disease activity. This study aimed to determine (i) the prevalence of prior and possible acute hepatitis E virus (HEV) infection among persons with chronic HBV and (ii) whether HEV infection is associated with liver disease flares among persons with chronic HBV. Methods Serum from a random sample of 600 adults in the Hepatitis B Research Network Cohort Study was tested for HEV RNA and anti-HEV IgM and IgG. Logistic regression models were used to estimate crude and adjusted odds ratios of anti-HEV prevalence for participant characteristics. Results Anti-HEV IgG and IgM seroprevalence was 28.5% and 1.7%, respectively. No participants had detectable HEV RNA. Of the 10 anti-HEV IgM+ participants, only 1 had elevated serum ALT at seroconversion. The odds of anti-HEV seropositivity (IgG+ or IgM+) were higher in older participants, males, Asians, less educated people, and those born outside the United States and Canada. Conclusions Acute HEV infection is a rare cause of serum ALT flares among persons with chronic HBV. The high seroprevalence of anti-HEV IgG among the chronic HBV patients is strongly associated with various demographic factors in this largely Asian American cohort.
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Affiliation(s)
- David R McGivern
- Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
| | - Hsing-Hua S Lin
- Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Junyao Wang
- Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Tiffany Benzine
- Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Mandana Khalili
- Department of Medicine, University of California San Francisco, San Francisco, California
| | - Mauricio Lisker-Melman
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Robert J Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Steven H Belle
- Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Michael W Fried
- UNC Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Ticehurst JR, Pisanic N, Forman MS, Ordak C, Heaney CD, Ong E, Linnen JM, Ness PM, Guo N, Shan H, Nelson KE. Probable transmission of hepatitis E virus (HEV) via transfusion in the United States. Transfusion 2019; 59:1024-1034. [PMID: 30702157 DOI: 10.1111/trf.15140] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Revised: 09/30/2018] [Accepted: 10/02/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) can inapparently infect blood donors. To assess transfusion transmission of HEV in the United States, which has not been documented, a donor-recipient repository was evaluated. STUDY DESIGN AND METHODS To identify donations that contained HEV RNA and were linked to patient-recipients with antibody evidence of HEV exposure, we assayed samples from the Retrovirus Epidemiology Donor Study (REDS) Allogeneic Donor and Recipient repository that represents 13,201 linked donations and 3384 transfused patients. Posttransfusion samples, determined to contain IgG anti-HEV by enzyme-linked immunosorbent assay, were reassayed along with corresponding pretransfusion samples for seroconversion (incident exposure) or at least fourfold IgG anti-HEV increase (reexposure). HEV-exposed patients were linked to donations in which HEV RNA was then detected by reverse-transcription quantitative polymerase chain reaction, confirmed by transcription-mediated amplification, and phylogenetically analyzed as subgenomic cDNA sequences. RESULTS Among all patients, 19 of 1036 (1.8%) who had IgG anti-HEV before transfusion were reexposed; 40 of 2348 (1.7%) without pretransfusion IgG anti-HEV seroconverted. These 59 patients were linked to 257 donations, 1 of which was positive by reverse-transcription quantitative polymerase chain reaction and transcription-mediated amplification. Plasma from this donation contained 5.5 log IU/mL of HEV RNA that grouped with HEV genotype 3, clade 3abchij. The patient-recipient of RBCs from this donation had a greater than eightfold IgG increase; however, clinical data are unavailable. CONCLUSIONS This is the first report of probable HEV transmission via transfusion in the United States, although it has been frequently observed in Europe and Japan. Additional data on the magnitude of the risk in the United States are needed.
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Affiliation(s)
- John R Ticehurst
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.,Division of Medical Microbiology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Nora Pisanic
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Michael S Forman
- Division of Medical Microbiology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Carly Ordak
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Christopher D Heaney
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | | | | | - Paul M Ness
- Division of Transfusion Medicine, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland.,Division of Oncology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Nan Guo
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Hua Shan
- Department of Transfusion Medicine, Stanford University, Palo Alto, California
| | - Kenrad E Nelson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.,Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland
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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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Cella E, Golkocheva-Markova E, Sagnelli C, Scolamacchia V, Bruni R, Villano U, Ciccaglione AR, Equestre M, Sagnelli E, Angeletti S, Ciccozzi M. Human hepatitis E virus circulation in Bulgaria: Deep Bayesian phylogenetic analysis for viral spread control in the country. J Med Virol 2019; 91:132-138. [PMID: 30168583 DOI: 10.1002/jmv.25296] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 07/07/2018] [Indexed: 12/23/2022]
Abstract
Hepatitis E virus (HEV) infection in Bulgaria is endemic, as demonstrated by the seroprevalence of antibody against the virus in the general population and by the high prevalence of clinical cases registered. In this study, a deep Bayesian phylogenetic analysis has been performed to provide information on the genetic diversity and the spread of HEV genotypes in Bulgaria. Three different data sets of HEV virus was built for genotyping by the maximum likelihood method, for evolutionary rate estimated by Bayesian Markov Chain Monte Carlo approach, for demographic history investigation and for selective pressure analysis. The evolutionary rate for genotype 3e, was 351 × 10-3 substitution/site/year (95% highest posterior density [95% HPD]: 145 × 10 -3 -575 × 10 -3 ). The root of the time to the most recent common ancestor of the Bayesian maximum clade credibility tree of HEV 3e genotype corresponded to 1965 (HPD 95% 1949-1994). The Bulgarian sequences mainly clustered in the main clade (clade A). The monophyletic clade included all Bulgarian genotype 3e sequences. The demographic history showed a slight growth from 1995 to 2000, followed by a sort of bottleneck in 2010s, a peak in 2011 and a new growth to 2015. Selection pressure analysis did not show sites under positive pressure but 64 statistically significant sites under negative selection. Molecular epidemiological surveillance by Bayesian phylogeny of HEV virus can contribute to trace the way of human infection after contact with swine source directly or heating meat improving public health control.
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Affiliation(s)
- Eleonora Cella
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Elitsa Golkocheva-Markova
- NRL of Viral Hepatitis, Virology Department, National Center of Infectious and Parasitic Diseases (NCIPD), Sofia, Bulgaria
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Vittoria Scolamacchia
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Roberto Bruni
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Umbertina Villano
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Anna Rita Ciccaglione
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Michele Equestre
- Department of Neurosciences, Istituto Superiore di Sanità, Rome, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
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Tripathy AS, Puranik S, Sharma M, Chakraborty S, Devakate UR. Hepatitis E virus seroprevalence among blood donors in Pune, India. J Med Virol 2018; 91:813-819. [PMID: 30489644 DOI: 10.1002/jmv.25370] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 11/24/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Blood transfusion is a recently reported route of hepatitis E virus (HEV) transmission. It is a bigger concern in regions where large-scale HEV genotype 1 infections occur causing more severe disease. The present study aims to assess the prevalence and rate of HEV infection in the blood donors of Pune, India. MATERIALS AND METHODS A total of 2447 healthy blood donors were screened for anti-HEV IgG and IgM antibodies. Anti-HEV IgM antibody positives were further subjected to alanine aminotransferase measurement, HEV RNA detection, viral load quantification and phylogenetic analysis. RESULTS Anti-HEV seroprevalence rate was 17.70%, while IgM prevalence rate was 0.20%. An age dependent increase in IgG seropositive rate was observed. Two of five IgM-positives tested positive for HEV RNA. The viral load ranged from 3.5 × 104 to 4.6 × 105 copies/mL and belonged to HEV genotype 1. CONCLUSIONS HEV prevalence rate of 17.70% in the blood donors of Pune, India, a developing country, goes at par with the developed countries. Current data of 0.20% (5 of 2447) blood donors positive for anti-HEV IgM and two of them being HEV RNA positive suggest a need for consideration of cost-effective evaluation towards pooled HEV RNA testing in blood banks.
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Affiliation(s)
| | - Shaila Puranik
- Department of Pathology, B.J. Medical College and Sassoon General Hospitals, Pune, India
| | - Meenal Sharma
- Hepatitis Group, National Institute of Virology, Pune, Maharashtra, India
| | | | - Ujwal R Devakate
- Department of Pathology, B.J. Medical College and Sassoon General Hospitals, Pune, India
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Horvatits T, Ozga AK, Westhölter D, Hartl J, Manthey CF, Lütgehetmann M, Rauch G, Kriston L, Lohse AW, Bendall R, Wedemeyer H, Dalton HR, Pischke S. Hepatitis E seroprevalence in the Americas: A systematic review and meta-analysis. Liver Int 2018; 38:1951-1964. [PMID: 29660259 DOI: 10.1111/liv.13859] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 04/05/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti-hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure. METHODS We performed a systematic review and meta-analysis. Literature search was performed in PubMed for articles published 01/1994-12/2016. Prevalence was estimated using a mixed-effects model and reported in line with PRISMA reporting guidelines. RESULTS Seroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06-3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%-15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%-7.1%; OR: 2.27 (1.25-4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15-81.61); P = .04). A comparison with published data from Europe demonstrated that anti-hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81-2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45-0.98), P = .04). CONCLUSIONS Hepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure.
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Affiliation(s)
- Thomas Horvatits
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ann-Kathrin Ozga
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dirk Westhölter
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Johannes Hartl
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Carolin F Manthey
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute of Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, Hamburg, Germany
| | - Geraldine Rauch
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany
| | - Levente Kriston
- Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, Hamburg, Germany
| | - Richard Bendall
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro, UK
| | - Heiner Wedemeyer
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, Hamburg, Germany.,Department of Gastroenterology, Hepatology, University Hospital of Essen, Essen, Germany
| | - Harry R Dalton
- Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro, UK
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, Hamburg, Germany
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46
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Hardtke S, Rocco R, Ogata J, Braga S, Barbosa M, Wranke A, Doi E, da Cunha D, Maluf E, Wedemeyer H, Muzzillo D. Risk factors and seroprevalence of hepatitis E evaluated in frozen-serum samples (2002-2003) of pregnant women compared with female blood donors in a Southern region of Brazil. J Med Virol 2018; 90:1856-1862. [DOI: 10.1002/jmv.25274] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 07/07/2018] [Indexed: 12/28/2022]
Affiliation(s)
- S. Hardtke
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig; Hannover Germany
| | - R. Rocco
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - J. Ogata
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - S. Braga
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - M. Barbosa
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - A. Wranke
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
| | - E. Doi
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig; Hannover Germany
| | - D. da Cunha
- Serology Lab, Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - E. Maluf
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
| | - H. Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig; Hannover Germany
| | - D. Muzzillo
- Department of Internal Medicine; Clinics Hospital, Federal University of Paraná; Curitiba Brazil
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Abstract
Why certain viruses cross the physical barrier of the human placenta but others do not is incompletely understood. Over the past 20 years, we have gained deeper knowledge of intrauterine infection and routes of viral transmission. This review focuses on human viruses that replicate in the placenta, infect the fetus, and cause birth defects, including rubella virus, varicella-zoster virus, parvovirus B19, human cytomegalovirus (CMV), Zika virus (ZIKV), and hepatitis E virus type 1. Detailed discussions include ( a) the architecture of the uterine-placental interface, ( b) studies of placental explants ex vivo that provide insights into the infection and spread of CMV and ZIKV to the fetal compartment and how these viruses undermine early development, and ( c) novel treatments and vaccines that limit viral replication and have the potential to reduce dissemination, vertical transmission and the occurrence of congenital disease.
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Affiliation(s)
- Lenore Pereira
- Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, California 94143, USA;
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48
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Grewal P, Ahmad J. Beware of HCV and HEV in Patients with Suspected Drug-Induced Liver Injury. ACTA ACUST UNITED AC 2018; 17:270-275. [PMID: 30766771 DOI: 10.1007/s11901-018-0410-1] [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] [Indexed: 12/17/2022]
Abstract
Purpose of Review- Without a specific biomarker the diagnosis of drug-induced liver injury (DILI) relies on exclusion of other causes of liver injury. This review examines the importance of testing for hepatitis C (HCV) and hepatitis E (HEV) in patients with suspected DILI. Recent Findings- Several national DILI registries have reported HCV and HEV infection in patients initially diagnosed with DILI. Particularly in patients with suspected DILI who have acute hepatocellular liver injury, acute HCV and acute HEV infection should be considered even in the absence of traditional risk factors. For HCV infection, testing for HCV RNA and HCV antibody are recommended. For HEV, the high prevalence of HEV IgG antibody means that HEV IgM antibody testing is suggested to exclude this infection. Summary- There should be a high clinical suspicion for acute HCV and HEV infection in patients with acute hepatocellular liver injury suspected of being due to DILI.
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Affiliation(s)
- Priya Grewal
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029
| | - Jawad Ahmad
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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49
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An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens. Adv Anat Pathol 2018; 25:273-281. [PMID: 29697415 DOI: 10.1097/pap.0000000000000195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non-E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.
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50
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Gu M, Qiu J, Guo D, Xu Y, Liu X, Shen C, Dong C. Evaluation of candidate genes associated with hepatitis A and E virus infection in Chinese Han population. Virol J 2018; 15:47. [PMID: 29558945 PMCID: PMC5859746 DOI: 10.1186/s12985-018-0962-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 03/12/2018] [Indexed: 01/13/2023] Open
Abstract
Background Recent GWAS-associated studies reported that single nucleotide polymorphisms (SNPs) in ABCB1, TGFβ1, XRCC1 genes were associated with hepatitis A virus (HAV) infection, and variants of APOA4 and APOE genes were associated with and hepatitis E virus (HEV) infection in US population. However, the associations of these loci with HAV or HEV infection in Chinese Han population remain unclear. Methods A total of 3082 Chinese Han persons were included in this study. Anti-HAV IgG and anti-HEV IgG were detected by enzyme-linked immunosorbent assay (ELISA). Genotypes in ABCB1, TGFβ1, XRCC1, APOA4 and APOE SNPs were determined by TaqMan MGB technology. Results In Chinese Han population, rs1045642 C to T variation in ABCB1 was significantly associated with the decreased risk of HAV infection (P < 0.05). However, the effect direction was different with the previous US study. Rs1001581 A to G variation in XRCC1, which was not identified in US population, was significantly associated with the protection against HAV infection in our samples (P < 0.05). In addition, our results suggested that rs7412 C to T variation in APOE was significantly associated with lower risk of HEV infection in males (adjusted OR < 1.0, P < 0.05) but not in females. Conclusions ABCB1 and XRCC1 genes variants are significantly associated with the protection against HAV infection. Additionally, Chinese Han males with rs7412 C to T variation in APOE gene are less prone to be infected by HEV. Electronic supplementary material The online version of this article (10.1186/s12985-018-0962-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maolin Gu
- Huai'an Forth Hospital, Huai'an, China
| | - Jing Qiu
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China
| | - Daoxia Guo
- Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Road, Nanjing, 211166, China
| | | | | | - Chong Shen
- Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Road, Nanjing, 211166, China.
| | - Chen Dong
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China.
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