Hepatitis E Virus (HEV) and Other Hepeviridae

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 15270

Special Issue Editors


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Laboratório de Gastroenterologia e Hepatologia Tropical—LIM/07, Departamento de Gastroenterologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 500, São Paulo 05403-000, SP, Brazil
Interests: virology; hepatology; molecular pathology

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Laboratório de Microbiologia Molecular, Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo 93525-075, Brazil
Interests: emerging viruses; pandemic preparedness; one-health
Special Issues, Collections and Topics in MDPI journals

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Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, Brazil
Interests: virology; hepatology; parvovirus

Special Issue Information

Dear Colleagues,

Hepatitis E Virus is one the five viruses reported worldwide that are considered to be primarily hepatotropic. It is associated with widespread viral hepatitis outbreaks and with severe cases in pregnant women. It is classified in the family Hepeviridae that includes two subfamilies, five genera, and ten species that infect fishes, mammals, and birds. Human HEV is classified in the Orthohepevirinae subfamily, and some of these viruses also infect other mammalian species, such as pigs, wild boars, deer, and camels, and can be considered zoonotic. These viruses can be detected via different serological and molecular ways. The aim of this Special Issue is to analyze the presence of human and animal infections by viruses belonging to the family Hepeviridae, analyze the different methodologies used for their detection, and use phylodynamics methodologies to analyze their distribution around the world and possible transmission routes. Original papers and reviews dealing with viruses belonging to this family dealing with virological aspects, new hosts species, and new human or animal populations infected with them will be welcomed.

Dr. João Renato Rebello Pinho
Dr. Fernando Spilki
Dr. Marcelo Alves Pinto
Guest Editors

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Keywords

  • hepatitis E
  • zoonosis
  • Hepeviridae
  • epidemiology
  • diagnosis
  • vaccines
  • treatment
  • natural history
  • phylodynamics

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Published Papers (6 papers)

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Research

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13 pages, 753 KiB  
Article
Serological Evidence of Hepatitis E Virus Infection in Brazilian Equines
by Caroline Roberta Soares Salgado, Aldaleia do Nascimento e Silva, Igor Falco Arruda, Patrícia Riddell Millar, Maria Regina Reis Amendoeira, Luciane Almeida Amado Leon, Raffaella Bertoni Cavalcanti Teixeira, Jorge Tiburcio Barbosa de Lima, Flávia Löwen Levy Chalhoub, Ana Maria Bispo de Filippis, Ana Beatriz Monteiro Fonseca, Jaqueline Mendes de Oliveira, Marcelo Alves Pinto and Andreza Soriano Figueiredo
Microorganisms 2023, 11(11), 2743; https://doi.org/10.3390/microorganisms11112743 - 10 Nov 2023
Viewed by 1750
Abstract
Hepatitis E virus (HEV) infection has been demonstrated in various animal species; those recognized as potential zoonotic reservoirs pose a considerable risk to public health. In Brazil, HEV-3 is the only genotype identified in humans and swine nationwide, in a colony-breeding cynomolgus monkey [...] Read more.
Hepatitis E virus (HEV) infection has been demonstrated in various animal species; those recognized as potential zoonotic reservoirs pose a considerable risk to public health. In Brazil, HEV-3 is the only genotype identified in humans and swine nationwide, in a colony-breeding cynomolgus monkey and, recently, in bovines and capybara. There is no information regarding HEV exposure in the equine population in Brazil. This study aimed to investigate anti-HEV antibodies and viral RNA in serum samples from horses slaughtered for meat export and those bred for sport/reproduction purposes. We used a commercially available ELISA kit modified to detect species-specific anti-HEV, using an anti-horse IgG-peroxidase conjugate and evaluating different cutoff formulas and assay precision. Serum samples (n = 257) were tested for anti-HEV IgG and HEV RNA by nested RT-PCR and RT-qPCR. The overall anti-HEV seroprevalence was 26.5% (68/257) without the detection of HEV RNA. Most municipalities (53.3%) and farms (58.8%) had positive horses. Animals slaughtered for human consumption had higher risk of HEV exposure (45.5%) than those bred for sports or reproduction (6.4%) (p < 0.0001). The statistical analysis revealed sex and breeding system as possible risk-associated factors. The first serological evidence of HEV circulation in Brazilian equines reinforces the need for the surveillance of HEV host expansion in a one-health approach. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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14 pages, 1568 KiB  
Article
Epidemiology of HEV Infection in Blood Donors in Southern Switzerland
by Stefano Fontana, Paolo Ripellino, Christoph Niederhauser, Nadja Widmer, Peter Gowland, Orlando Petrini, Manuela Aprile, Giorgio Merlani and Florian Bihl
Microorganisms 2023, 11(10), 2375; https://doi.org/10.3390/microorganisms11102375 - 22 Sep 2023
Cited by 2 | Viewed by 1279
Abstract
From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM [...] Read more.
From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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9 pages, 768 KiB  
Article
Evaluation of Non-Invasive Sampling Methods for Detection of Hepatitis E Virus Infected Pigs in Pens
by Marina Meester, Aniek Rademaker, Martijn Bouwknegt, Renate W. Hakze-van der Honing, Arjan Stegeman, Wim H. M. van der Poel and Tijs J. Tobias
Microorganisms 2023, 11(2), 500; https://doi.org/10.3390/microorganisms11020500 - 16 Feb 2023
Viewed by 1950
Abstract
Pigs are a reservoir of hepatitis E virus (HEV), which causes hepatitis in humans. To study the epidemiology of HEV in pig farms, sampling methods are currently used that cause discomfort to pigs, such as rectal sampling. In line with the 3Rs principle, [...] Read more.
Pigs are a reservoir of hepatitis E virus (HEV), which causes hepatitis in humans. To study the epidemiology of HEV in pig farms, sampling methods are currently used that cause discomfort to pigs, such as rectal sampling. In line with the 3Rs principle, we aimed to evaluate non-invasive methods to detect pens with HEV-shedding pigs. Twenty-eight pens of one farm were sampled cross-sectionally. Individual rectal swabs (IRS) were collected to determine prevalence within pens. Four pen-level samples were compared: a pool of IRS per pen (P), boot socks (BS), oral fluid (OF) and pooled faecal droppings (FD). Each sample was tested by RT-PCR and the sensitivity and specificity of each method was determined by Bayesian latent class analysis. According to IRS, 19/28 pens were HEV positive. BS had a sensitivity of 95% and detected HEV in pens with 10% of pigs shedding; however, specificity was below 30%. FD were comparably accurate to P, with a sensitivity and specificity of 94% and 86%, respectively. BS sampling is thus advised to detect early shedding of HEV or pen contamination, and FD to determine the duration of shedding. This study demonstrates that non-invasive sampling can replace rectal swabs in research on HEV in pigs. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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10 pages, 2354 KiB  
Communication
Phylodynamic Analysis Suggests That Deer Species May Be a True Reservoir for Hepatitis E Virus Genotypes 3 and 4
by Anastasia A. Karlsen, Vera S. Kichatova, Karen K. Kyuregyan and Mikhail I. Mikhailov
Microorganisms 2023, 11(2), 375; https://doi.org/10.3390/microorganisms11020375 - 1 Feb 2023
Cited by 3 | Viewed by 1627
Abstract
Hepatitis E virus (HEV) genotypes 3 and 4 (HEV-3 and HEV-4) cause zoonotic infection in humans, with domestic pigs and wild boars being the main reservoirs of infection. Other than suids, HEV-3 and HEV-4 are found in ruminants, most frequently in deer species. [...] Read more.
Hepatitis E virus (HEV) genotypes 3 and 4 (HEV-3 and HEV-4) cause zoonotic infection in humans, with domestic pigs and wild boars being the main reservoirs of infection. Other than suids, HEV-3 and HEV-4 are found in ruminants, most frequently in deer species. However, it is still debatable, whether HEV infection in deer is a spillover, or indicates a stable virus circulation in these host species. To explore the patterns of HEV-3 and HEV-4 transmission in deer and other host species, we performed a Bayesian analysis of HEV sequences available in GenBank. A total of 27 HEV sequences from different deer species were found in GenBank. Sequences from wild boars collected in the same territories, as well as sequences from all mammals that were most similar to sequences from deer in blast search, were added to the dataset, comprising 617 in total sequences. Due to the presence of partial genomic sequences, they were divided into four subsets (two ORF1 fragments and two ORF2 fragments) and analyzed separately. European HEV-3 sequences and Asian HEV-4 sequences collected from deer species demonstrated two transmission patterns. The first pattern was spillover infection, and the second pattern was deer-to-deer transmission, indicating stable HEV circulation in these species. However, all geographic HEV clusters that contained both deer and swine sequences originated from ancestral swine strains. HEV-3 and HEV-4 transmission patterns in ungulates reconstructed by means of Bayesian analysis indicate that deer species are a true host for HEV. However, wild and domestic swine are often the primary source of infection for ruminants living in the same areas. Complete HEV genomic sequences from different parts of the world are crucial for further understanding the HEV-3 and HEV-4 circulation patterns in wildlife. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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19 pages, 2454 KiB  
Article
A Randomized Large-Scale Cross-Sectional Serological Survey of Hepatitis E Virus Infection in Belgian Pig Farms
by Constance Wielick, Louisa Ludwig-Begall, Christel Faes, Stefaan Ribbens, Claude Saegerman and Etienne Thiry
Microorganisms 2023, 11(1), 129; https://doi.org/10.3390/microorganisms11010129 - 4 Jan 2023
Cited by 1 | Viewed by 2437
Abstract
Hepatitis E virus (HEV) is the causative agent of hepatitis E disease in humans. While sporadic HEV infections, which occur in industrialised countries and are typically due to HEV genotypes 3 or 4, are asymptomatic and self-limiting, a chronic form of the disease [...] Read more.
Hepatitis E virus (HEV) is the causative agent of hepatitis E disease in humans. While sporadic HEV infections, which occur in industrialised countries and are typically due to HEV genotypes 3 or 4, are asymptomatic and self-limiting, a chronic form of the disease can lead to liver cirrhosis in immunocompromised individuals. Pigs share HEV 3 and 4 genotypes and are thus considered a major animal reservoir for human infection. A subset of animals has been shown to carry HEV particles at the age of slaughter, rendering raw or undercooked pig products potential vectors for human infection. To provide an overview of the current dissemination of HEV in Belgian pig herds, this study was designed as a randomized, robust, large-scale, cross-sectional, serological survey. HEV genotypes and subtypes recently circulating in Belgium (2020–2021) were investigated. Sample stratification as well as epidemiological investigation through the available demographic data of the sampled herds showed that HEV widely circulated in the Belgian pig population during this time and that a change in the circulating HEV strains may have occurred in the last decade. Herd size and type were identified as risk factors for HEV herd-seropositivity. Identifying farms at risk of being HEV-positive is an important step in controlling HEV spread and human infection. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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Review

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14 pages, 1299 KiB  
Review
The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection—A Condition Affecting Immunocompromised Patients
by Satoshi Takakusagi, Satoru Kakizaki and Hitoshi Takagi
Microorganisms 2023, 11(5), 1303; https://doi.org/10.3390/microorganisms11051303 - 16 May 2023
Cited by 9 | Viewed by 4711
Abstract
Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause [...] Read more.
Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7—usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments—such as ribavirin—should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) and Other Hepeviridae)
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