Hepatitis E Virus, an Emergent Foodborne Pathogen? Public Health Implications

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

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 27790

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Co-Guest Editor
Centro de Vigilancia Sanitaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain
Interests: microbiology; veterinary microbiology; hepatitis E virus; One Health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatitis E virus (HEV) is one of the main causes of viral acute hepatitis in humans worldwide. The origin of HEV infection in humans in industrialized countries is linked to direct contact with infected animals or to the consumption of raw or undercooked meat and liver, particularly of pig origin. Likewise, the presence of HEV has been described also in other livestock animals, fruits and vegetables, and mollusks. New epidemiological evidence presents HEV as a relevant emerging food-borne zoonotic disease in Europe. Indeed, over the last 10 years, the reported cases have increased 10 times, even though HEV is considered an underdiagnosed and underreported disease. Most cases are associated with the consumption of raw or undercooked meat and liver pork products. Taking into account that pork meat is the major type of meat produced in EU/EEA countries and that European pork meat exportation balance is very positive, the implications at European level for both the market and the consumers could be extremely serious, especially after the press coverage in UE, particularly in UK, linking pig products with cases of HEV infection. Thus, not only animal and human health professionals and porcine producers are concerned about HEV, but also the general population. Consequently, EFSA has recently published a scientific report that highlights the high increase of HE cases in Europe and emphasizes the need for more research efforts on the epidemiology, diagnosis, and control of HEV. In this Special Issue, we will present the more relevant advances in epidemiology, diagnosis, and control of this virus.

Dr. David Rodríguez-Lázaro
Dr. Nereea García-Benzaquén
Guest Editors

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Keywords

  • Hepatitis E virus 
  • Epidemiology 
  • Control 
  • Diagnosis

Published Papers (9 papers)

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Research

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7 pages, 457 KiB  
Communication
Hepatitis E Virus in Manure and Its Removal by Psychrophilic anaerobic Biodigestion in Intensive Production Farms, Santa Catarina, Brazil, 2018–2019
by Doris Sobral Marques Souza, Deisi Cristine Tápparo, Paula Rogovski, Rafael Dorighello Cadamuro, Estêvão Brasiliense de Souza, Raphael da Silva, Roberto Degenhardt, Juliano De Dea Lindner, Aline Viancelli, William Michelon, Airton Kunz, Helen Treichel, Marta Hernández, David Rodríguez-Lázaro and Gislaine Fongaro
Microorganisms 2020, 8(12), 2045; https://doi.org/10.3390/microorganisms8122045 - 21 Dec 2020
Cited by 6 | Viewed by 3127
Abstract
Hepatitis E virus (HEV) is an important enteric agent that can circulate in swine; it is excreted in manure, and of zoonotic interest. The present study investigated, by RT-qPCR, the circulation of HEV in swine manure from different types of pig farms (maternity, [...] Read more.
Hepatitis E virus (HEV) is an important enteric agent that can circulate in swine; it is excreted in manure, and of zoonotic interest. The present study investigated, by RT-qPCR, the circulation of HEV in swine manure from different types of pig farms (maternity, nursery, and grow-finish farms) in Santa Catarina State, the major pig production area of Brazil, and also evaluated the HEV removal efficiency of psychrophilic anaerobic biodigesters (PABs). While HEV was consistently detected in manure from grow-finish pig farms (>4 log HEV genome copies (GC) L−1), the virus was not detected in manure from maternity and nursery farms. These findings suggest a potential high biosafety status during primary-swine production, with a subsequent contamination in grow-finish production. The anaerobic biodigestion process reduced more than 2 log10 HEV GC in the processed swine manure. However, the virus concentration in final effluent remained high, with an average value of 3.85 log10 HEV GC L−1. Consequently, our results demonstrate that PABs can be a robust tool for effective inactivation of HEV, while reinforcing the need for sanitary surveillance and legislation of swine manure-derived biofertilizers, to avoid the spread of zoonotic enteric pathogens such as HEV. Full article
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15 pages, 294 KiB  
Article
Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
by Milagros Muñoz-Chimeno, Alejandro Cenalmor, Maira Alejandra Garcia-Lugo, Marta Hernandez, David Rodriguez-Lazaro and Ana Avellon
Microorganisms 2020, 8(9), 1417; https://doi.org/10.3390/microorganisms8091417 - 15 Sep 2020
Cited by 14 | Viewed by 2389
Abstract
The hepatitis E virus (HEV) hypervariable region (HVR) presents the highest divergence of the entire HEV genome. It is characteristically rich in proline, and so is also known as the “polyproline region” (PPR). HEV genotype 3 (HEV-3) exhibits different PPR lengths due to [...] Read more.
The hepatitis E virus (HEV) hypervariable region (HVR) presents the highest divergence of the entire HEV genome. It is characteristically rich in proline, and so is also known as the “polyproline region” (PPR). HEV genotype 3 (HEV-3) exhibits different PPR lengths due to insertions, PPR and/or RNA-dependent RNA polymerase (RdRp) duplications and deletions. A total of 723 PPR-HEV sequences were analyzed, of which 137 HEV-3 sequences were obtained from clinical specimens (from acute and chronic infection) by Sanger sequencing. Eight swine stool/liver samples were also analyzed. N- and C-terminal fragments were confirmed as being conserved, but they harbored differences between genotypes and were not proline-plentiful regions. The genuine PPR is the intermediate region between them. HEV-3 PPR contains a higher percentage (30.4%) of prolines than other genotypes. We describe for the first time: (1) the specific placement of HEV-3 PPR rearrangements in sites 1 to 14 of the PPR, noting that duplications are more frequently attached to sites 11 and 12 (AAs 74–79 and 113–118, respectively); (2) the cadence of repetitions follows a circular-like pattern of blocks A to J, with F, G, H, and I being the most frequent; (3) a previously unreported insertion homologous to apolipoprotein C1; and (4) the increase in frequency of potential N-glycosylation sites and differences in AAs composition related to duplications. Full article
10 pages, 812 KiB  
Article
Whole Genome Sequencing Characterization of HEV3-e and HEV3-f Subtypes among the Wild Boar Population in the Abruzzo Region, Italy: First Report
by Giuseppe Aprea, Silvia Scattolini, Daniela D’Angelantonio, Alexandra Chiaverini, Valeria Di Lollo, Sabrina Olivieri, Maurilia Marcacci, Iolanda Mangone, Stefania Salucci, Salvatore Antoci, Cesare Cammà, Adriano Di Pasquale, Giacomo Migliorati and Francesco Pomilio
Microorganisms 2020, 8(9), 1393; https://doi.org/10.3390/microorganisms8091393 - 11 Sep 2020
Cited by 11 | Viewed by 2277
Abstract
Hepatitis E virus (HEV) is an emergent zoonotic pathogen, causing worldwide acute and chronic hepatitis in humans. HEV comprises eight genotypes and several subtypes. HEV genotypes 3 and 4 (HEV3 and HEV4) are zoonotic. In Italy, the most part of HEV infections (80%) [...] Read more.
Hepatitis E virus (HEV) is an emergent zoonotic pathogen, causing worldwide acute and chronic hepatitis in humans. HEV comprises eight genotypes and several subtypes. HEV genotypes 3 and 4 (HEV3 and HEV4) are zoonotic. In Italy, the most part of HEV infections (80%) is due to autochthonous HEV3 circulation of the virus, and the key role played by wild animals is generally accepted. Abruzzo is an Italian region officially considered an HEV “hot spot”, with subtype HEV3-c being up to now the only one reported among wild boars. During the year 2018–2019, a group of wild boars in Abruzzo were screened for HEV; positive RNA liver samples were subjected to HEV characterization by using the whole genome sequencing (WGS) approach methodology. This represents the first report about the detection of HEV-3 subtypes e and f in the wild boar population in this area. Since in Italy human infections from HEV 3-e and f have been associated with pork meat consumption, our findings deserve more in-depth analysis with the aim of evaluating any potential correlation between wild animals, the pork chain production and HEV human infections. Full article
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16 pages, 1534 KiB  
Article
Assessment of the Presence of Hepatitis E Virus in Surface Water and Drinking Water in Portugal
by Daniel Salvador, Célia Neto, Maria João Benoliel and Maria Filomena Caeiro
Microorganisms 2020, 8(5), 761; https://doi.org/10.3390/microorganisms8050761 - 19 May 2020
Cited by 21 | Viewed by 3947
Abstract
Hepatitis E virus (HEV) is a non-enveloped single-stranded positive-sense RNA virus, belonging to the Hepeviridae family, resistant to environmental conditions, and transmitted by the consumption of contaminated water. This virus is responsible for both sporadic and epidemic outbreaks, leading to thousands of infections [...] Read more.
Hepatitis E virus (HEV) is a non-enveloped single-stranded positive-sense RNA virus, belonging to the Hepeviridae family, resistant to environmental conditions, and transmitted by the consumption of contaminated water. This virus is responsible for both sporadic and epidemic outbreaks, leading to thousands of infections per year in several countries, and is thus considered an emerging disease in Europe and Asia. This study refers to a survey in Portugal during 2019, targeting the detection and eventual quantification of enteric viruses in samples from surface and drinking water. Samples positive for HEV RNA were recurrently found by reverse transcription quantitative PCR (RT-qPCR), in both types of matrix. The infectivity of these samples was evaluated in cultured Vero E6 cells and RNA from putative viruses produced in cultures evidencing cytopathic effects and was subjected to RT-qPCR targeting HEV genomic RNA. Our results evidenced the existence of samples positive either for HEV RNA (77.8% in surface water and 66.7% in drinking water) or for infectious HEV (23.0% in surface water and 27.7% in drinking water). These results highlight the need for effective virological control of water for human consumption and activities. Full article
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10 pages, 597 KiB  
Article
Risk of Hepatitis E among Persons Who Inject Drugs in Hong Kong: A Qualitative and Quantitative Serological Analysis
by Siddharth Sridhar, Nicholas Foo-Siong Chew, Jianwen Situ, Shusheng Wu, Ernest Sing-Hong Chui, Athene Hoi-Ying Lam, Jian-Piao Cai, Vincent Chi-Chung Cheng and Kwok-Yung Yuen
Microorganisms 2020, 8(5), 675; https://doi.org/10.3390/microorganisms8050675 - 6 May 2020
Cited by 3 | Viewed by 2498
Abstract
Hepatitis E virus (HEV) is an important cause of hepatitis, which can be transmitted via the bloodborne route. However, risk of hepatitis E among persons who inject drugs (PWIDs) is poorly understood. This study aimed to elucidate whether PWIDs are at risk for [...] Read more.
Hepatitis E virus (HEV) is an important cause of hepatitis, which can be transmitted via the bloodborne route. However, risk of hepatitis E among persons who inject drugs (PWIDs) is poorly understood. This study aimed to elucidate whether PWIDs are at risk for hepatitis E. We performed HEV IgM, IgG and nucleic acid detection on a cohort of 91 PWIDs and 91 age- and sex-matched organ donors. Blood HEV IgG was measured using the WHO HEV antibody standard. The effects of age, gender and addictive injection use on HEV serostatus and concentration were assessed. HEV IgG seroprevalence was 42/91 (46.2%) in the PWID group and 20/91 (22%) in the donor group (odds ratio = 3.04 (1.59–5.79), p = 0.0006). The median HEV IgG concentration was 5.8 U/mL (IQR: 2.5–7.9) in the PWID group and 2.1 U/mL (IQR: 1.2–5.3) in the donor group (p = 0.005). Increasing age and addictive injection use were significantly associated with HEV IgG serostatus, but only addictive injection use was associated with HEV IgG concentration (p = 0.024). We conclude that PWIDs are at increased risk for hepatitis E and are prone to repeated HEV exposure and reinfection as indicated by higher HEV IgG concentrations. Full article
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10 pages, 468 KiB  
Article
Liver Transudate, a Potential Alternative to Detect Anti-Hepatitis E Virus Antibodies in Pigs and Wild Boars (Sus scrofa)
by Alejandro Navarro, Carmen Bárcena, Pilar Pozo, Alberto Díez-Guerrier, Irene Martínez, Coral Polo, Clara Duque, David Rodríguez-Lázaro, Joaquín Goyache and Nerea García
Microorganisms 2020, 8(3), 450; https://doi.org/10.3390/microorganisms8030450 - 23 Mar 2020
Cited by 5 | Viewed by 2799
Abstract
In recent years, cases of hepatitis E virus (HEV) infection have increased in Europe in association with the consumption of contaminated food, mainly from pork products but also from wild boars. The animal’s serum is usually tested for the presence of anti-HEV antibodies [...] Read more.
In recent years, cases of hepatitis E virus (HEV) infection have increased in Europe in association with the consumption of contaminated food, mainly from pork products but also from wild boars. The animal’s serum is usually tested for the presence of anti-HEV antibodies and viral RNA but, in many cases such as during hunting, an adequate serum sample cannot be obtained. In the present study, liver transudate was evaluated as an alternative matrix to serum for HEV detection. A total of 125 sera and liver transudates were tested by enzyme-linked immunosorbent assay at different dilutions (1:2, 1:10, 1:20), while 58 samples of serum and liver transudate were checked for the presence of HEV RNA by RT-qPCR. Anti- HEV antibodies were detected by ELISA in 68.0% of the serum samples, and in 61.6% of the undiluted transudate, and in 70.4%, 56.8%, and 44.8% of 1:2, 1:10, or 1:20 diluted transudate, respectively. The best results were obtained for the liver transudate at 1:10 dilution, based on the Kappa statistic (0.630) and intraclass correlation coefficient (0.841). HEV RNA was detected by RT-qPCR in 22.4% of the serum samples and 6.9% of the transudate samples, all samples used for RT-qPCR were positive by ELISA. Our results indicate that liver transudate may be an alternative matrix to serum for the detection of anti-HEV antibodies. Full article
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18 pages, 1476 KiB  
Article
Seroprevalence Study of Anti-HEV IgG among Different Adult Populations in Corsica, France, 2019
by Lisandru Capai, Shirley Masse, Pierre Gallian, Cécile Souty, Christine Isnard, Thierry Blanchon, Brigitte Peres, Xavier de Lamballerie, Rémi Charrel and Alessandra Falchi
Microorganisms 2019, 7(10), 460; https://doi.org/10.3390/microorganisms7100460 - 16 Oct 2019
Cited by 13 | Viewed by 3502
Abstract
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. In France, hyperendemic areas including Corsica have an anti-HEV Immunoglobulin G (IgG) prevalence higher than 50%. The aim of this study was to determine the seroprevalence of anti-HEV IgG in three [...] Read more.
Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. In France, hyperendemic areas including Corsica have an anti-HEV Immunoglobulin G (IgG) prevalence higher than 50%. The aim of this study was to determine the seroprevalence of anti-HEV IgG in three adult populations in Corsica and the risk factors associated with antibody detection. Between 2017 and 2019, a total of 930 individuals, including 467 blood donors, 393 students or university staff members and 70 patients from general practice, were tested for the presence of anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay kit and filled a questionnaire. The association between seropositivity and potential risk factors was tested with univariate and multivariate analyses. Out of the 930 samples, 52.3% (486/930) were seropositive—54.4% (254/467) among blood donors, 47.6% (187/393) among university students and 64.3% (45/70) among patients of general practice. Three main risk factors were identified: (i) skinning and butchering (Adjusted Odds Ratio aOR = 2.76, 95% confidence interval [95% CI] [1.51–5.37]; p-value < 10−3), (ii) consumption of a local pork live raw sausage (fittonu) (aOR = 1.95 95% CI [1.45–2.64]; p-value = 10−5), and (iii) increasing age (p-value = 0.003). Seropositivity rates between the different populations were homogeneous after age stratification. This cross-sectional study indicates a high anti-HEV IgG seroprevalence in the Corsican adult population, not significantly different between women and men and increasing with age. This serosurvey also showed homogeneity regarding the exposure to HEV among three different types of populations. Finally, we confirmed the endemicity of Corsica with respect to HEV and identified a strong association between consumption of figatellu/fittonu and the practice of skinning and butchering with the detection of anti-HEV IgG. Full article
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Review

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9 pages, 2280 KiB  
Review
Human Immunodeficiency Virus Infected Patients are Not at Higher Risk for Hepatitis E Virus Infection: A Systematic Review and Meta-Analysis
by Pedro Lopez-Lopez, Mario Frias, Angela Camacho, Antonio Rivero and Antonio Rivero-Juarez
Microorganisms 2019, 7(12), 618; https://doi.org/10.3390/microorganisms7120618 - 26 Nov 2019
Cited by 2 | Viewed by 2250
Abstract
Hepatitis E virus (HEV) infection is the most common cause of acute hepatitis in the world. It is not well established whether people infected with the human immunodeficiency virus (HIV) are more susceptible to infection with HEV than people not infected with HIV. [...] Read more.
Hepatitis E virus (HEV) infection is the most common cause of acute hepatitis in the world. It is not well established whether people infected with the human immunodeficiency virus (HIV) are more susceptible to infection with HEV than people not infected with HIV. Many studies have evaluated this relationship, although none are conclusive. The aim of this systematic review and meta-analysis was to assess whether patients with HIV infection constitute a risk group for HEV infection. A systematic review and meta-analysis was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), to find publications comparing HEV seroprevalences among HIV infected and uninfected populations. The analysis was matched by sex, age and geographical area, and compared patients who live with HIV and HIV-negative individuals. The odds ratio (OR) for patients with HIV was 0.87 (95% CI: 0.74–1.03) in the fixed effects meta-analysis and 0.88 (95% CI: 0.70–1.11) in random effects, with I2 = 47%. This study did not show that HIV infection was a risk factor for HEV infection when compared with those who are HIV-negative. Full article
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Other

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13 pages, 297 KiB  
Case Report
Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients
by Antonio Rivero-Juarez, Nicolau Vallejo, Pedro Lopez-Lopez, Ana Isabel Díaz-Mareque, Mario Frias, Aldara Vallejo, Javier Caballero-Gómez, María Rodríguez-Velasco, Esther Molina and Antonio Aguilera
Microorganisms 2020, 8(1), 51; https://doi.org/10.3390/microorganisms8010051 - 26 Dec 2019
Cited by 8 | Viewed by 3774
Abstract
The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this [...] Read more.
The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage. Full article
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