Search

Competing Interests: Competing interests: None declared.

Background & Aims: Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection., Methods: Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated., Results: We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model., Conclusions: HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Pigs are the natural host of HEV genotype 3 and the main reservoir of HEV. As the host range of HEV genotype 3 expands, the possibility that HEV from various species can be transmitted to humans via pigs is increasing. We investigated the potential cross-species transmission of HEV by infecting minipigs with swine HEV (swHEV), rabbit HEV (rbHEV), and human HEV (huHEV) and examining their histopathological characteristics and distribution in various organs. Fifteen specific-pathogen-free Yucatan minipigs were infected with swHEV, rbHEV, huHEV, or a mock control. In the present study, we analysed faecal shedding, viremia, and serological parameters over a seven-week period. Our results indicated that swHEV exhibited more robust shedding and viremia than non-swHEVs. Only swHEV affected the serological parameters, suggesting strain-specific differences. Histopathological examination revealed distinct patterns in the liver, pancreas, intestine, and lymphoid tissues after infection with each HEV strain. Notably, all three HEVs induced histopathological changes in the pancreas, supporting the association of HEVs with acute pancreatitis. Our results also identified skeletal muscle as a site of HEV antigen presence, suggesting a potential link to myositis. In conclusion, this study provides valuable insights into the infection dynamics of different HEV strains in minipigs, emphasizing the strain-specific variations in virological, serological, and histological parameters. The observed differences in infection kinetics and tissue tropism will contribute to our understanding of HEV pathogenesis and the potential for cross-species transmission., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions ("naked") found in infected hosts' feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review.

Background: Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation., Case Presentation: Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log 10 IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment., Discussion: Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA., (© 2024. The Author(s).)

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG&#95;23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG&#95;23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3-80.9%). Conversely, it displayed lower similarity (73.3-78.1%) with the HEV-1-5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG&#95;23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG&#95;23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG&#95;23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV associated pregnancy mortality has been reported as up to 30% in humans. Recent findings suggest HEV may elicit effects directly in the reproductive system with HEV protein found in the testis, viral RNA in semen, and viral replication occurring in placental cell types. Using a natural host model for HEV infection, pigs, we demonstrate infectious HEV within the mature spermatozoa and altered sperm viability from HEV infected pigs. HEV isolated from sperm remained infectious suggesting a potential transmission route via sexual partners. Our findings suggest that HEV should be explored as a possible sexually transmittable disease. Our findings propose that infection routes outside of oral and intravenous infection need to be considered for their potential to contribute to higher mortality in HEV infections when pregnancy is involved and in HEV disease in general., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Yadav et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients., Aims: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted., Methods: All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available., Results: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection., Conclusion: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.

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.

Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas ® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.

In Japan, hepatitis E virus (HEV) causes hepatitis in humans through the consumption of raw or undercooked meat, including game meat. In the present study, nationwide surveillance of HEV infection among a total of 5,557 wild animals, including 15 species, was conducted in Japan. The prevalence of anti-HEV antibodies in wild boar was 12.4%, with higher positive rates in big boars (over 50 kg, 18.4%) than in small individuals (less than 30 kg, 5.3%). Furthermore, HEV RNA was more frequently detected in piglets than in older boars. Interestingly, the detection of HEV among wildlife by ELISA and RT-PCR suggested that HEV infection in Sika deer was a very rare event, and that there was no HEV infection among wild animals except for wild boar, Sika deer and Japanese monkeys. In conclusion, wild boar, especially piglets, are at high risk of HEV infection, while other wild animals showed less risk or no risk of HEV transmission.

Humans can become infected with hepatitis E virus (HEV) by consumption of undercooked pork. To reduce the burden of HEV in humans, mitigation on pig farms is needed. HEV is found on most pig farms globally, yet within-farm seroprevalence estimates vary considerably. Understanding of the underlying variation in infection dynamics within and between farms currently lacks. Therefore, we investigated HEV infection dynamics by sampling 1711 batches of slaughter pigs from 208 Dutch farms over an 8-month period. Four farm types, conventional, organic, and two types with strict focus on biosecurity, were included. Sera were tested individually with an anti-HEV antibody ELISA and pooled per batch with PCR. All farms delivered seropositive pigs to slaughter, yet batches (resembling farm compartments) had varying results. By combining PCR and ELISA results, infection moment and extent per batch could be classified as low transmission, early, intermediate or late. Cluster analysis of batch infection moments per farm resulted in four clusters with distinct infection patterns. Cluster 1 farms delivered almost exclusively PCR negative, ELISA positive batches to slaughter (PCR - ELISA + ), indicating relatively early age of HEV infection. Cluster 2 and 3 farms delivered 0.3 and 0.7 of batches with intermediate infection moment (PCR + ELISA + ) respectively and only few batches with early infection. Cluster 4 farms delivered low transmission (PCR - ELISA - ) and late infection (PCR + ELISA - ) batches, demonstrating that those farms can prevent or delay HEV transmission to farm compartments. Farm type partly coincided with cluster assignment, indicating that biosecurity and management are related to age of HEV infection., (© 2022. The Author(s).)

Background and Aims: Immunocompromised patients are at risk of chronic hepatitis E which can be acquired by blood transfusions. Currently, screening of blood donors (BDs) for HEV RNA with a limit of detection (LOD) of 2,000 IU/ml is required in Germany. However, this may result in up to 440,000 IU of HEV RNA in blood products depending on their plasma volume. We studied the residual risk of transfusion-transmitted (tt) HEV infection when an LOD of 2,000 IU/ml is applied., Methods: Highly sensitive individual donor testing for HEV RNA on the Grifols Procleix Panther system (LOD 7.89 IU/ml) was performed. HEV loads were quantified by real-time PCR., Results: Of 16,236 donors, 31 (0.19%) were HEV RNA positive. Three BDs had viral loads between 710 and 2,000 IU/ml, which pose a significant risk of tt hepatitis E with any type of blood product. Eight BDs had viral loads of >32 to 710 IU/ml, which pose a risk of tt hepatitis E with platelet or plasma transfusions because of their higher plasma volume compared to red blood cell concentrates. Eight of these 11 potentially infectious BDs were seronegative for HEV, indicating a recent infection. Only 8 of 31 donors had viral loads >2,000 IU/ml that would also have been detected by the required screening procedure and 12 had very low HEV loads (<32 IU/ml)., Conclusions: Screening of BDs with an LOD of 2,000 IU/ml reduced the risk of tt HEV infection by about 73% for red blood cell concentrates but by just 42% for platelet and fresh frozen plasma transfusions. Single donor screening (LOD <32 IU/ml) should lead to an almost 100% risk reduction., Lay Summary: Immunocompromised patients, such as solid organ or hematopoietic stem cell recipients, are at risk of chronic hepatitis E, which can be acquired via blood transfusions. The risk of transfusion-transmitted hepatitis E in these patients may not be sufficiently controlled by (mini-)pool hepatitis E virus RNA screening of blood donors. Single donor screening should be considered to improve the safety of blood products., Competing Interests: Conflicts of interest A.H. received a travel grant from Grifols Inc. All other authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) infection is an emerging zoonotic viral disease, with an increasingly international public health challenge. Despite the concerns that the global disease burden may be underestimated. Therefore, evaluation of the disease epidemiology in South - eastern Asia through a systematic review will assist in unraveling the burden of the disease in the subregion. A priori protocol was prepared for the systematic review and followed by a literature search involving five electronic databases. Identified publications were screened for high quality studies and the elimination of bias and relevant data extracted. A total of 4157 citations were captured, and only 35 were included in the review. A wide range of HEV seroprevalence was recorded from 2% (urban blood donors in Malaysia) to 77.7% (lowland communities in Lao PDR). Sporadic HEV infection and epidemics were also detected in the subregion. Indicating hyperendemicity of the disease in South - eastern Asia.

Background: Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province., Methods: We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness., Results: From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R 2  = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days)., Conclusions: HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.

Hepatitis E virus (HEV) is a major causative agent of acute viral hepatitis in many regions of the world including Africa. In Cameroon, there is no published molecular study on HEV in humans. However, based on serological assays, the first outbreak of HEV was detected in North-Cameroon. The objective of this study was to determine the molecular characterization of HEV that circulated during this period. A retrospective study design was used to select serum samples among those collected during the outbreak period. immunoglobulin M positive samples available in sufficient volumes to amplify HEV RNA were selected. RNA was extracted and then amplified by a real-time reverse transcription polymerase chain reaction (real time RT-PCR) assay, followed by a nested reverse transcription polymerase chain reaction (nested RT-PCR) assay for sequencing and phylogenetic analysis. Overall, 24 samples were selected and HEV RNA was amplified by real-time RT-PCR in 20 samples. Amongst these, 12 samples were positive for HEV RNA by nested RT-PCR and yielded good sequencing products. Phylogenetic analysis showed that 10 samples clustered with HEV genotype 1 (subtype 1e) and two samples clustered with HEV genotype 3 (subtype 3f). This study fills the gap of knowledge on the molecular epidemiology of HEV in Cameroon and confirms the first report of the hepatitis E outbreak in North-Cameroon., (© 2020 Wiley Periodicals LLC.)

Hepatitis E, a public health concern in developing countries, frequently presents in epidemic, as well as in sporadic forms. This study investigated an outbreak of viral hepatitis at Yavatmal, Maharashtra, India in March 2019. Blood samples from 10 patients were received at Indian Council of Medical Research-National Institute of Virology, Pune to test for the presence of enterically transmitted hepatitis viruses. Subsequently, 49 suspected cases were screened for anti-hepatitis E virus (HEV)/hepatitis A virus (HAV) immunoglobulin M and immunoglobulin G (IgG) antibodies, alanine amino-transferase levels and HEV RNA. Water samples were screened for HEV and HAV RNA followed by phylogenetic analysis. Overall 32 of 49 (65.3%) suspected cases had recent acute HEV infection, while dual infection with HAV was noted in one case (2.04%). Forty-eight of 49 suspected cases were positive for anti-HAV IgG antibodies indicative of previously acquired immunity against HAV. Water samples had evidence of HEV contamination as detected by reverse transcription-polymerase chain reaction. Sequencing of HEV RNA from both patients (n = 2) and water samples (n = 5) indicated HEV genotype 1 to be the etiological agent of this outbreak. Serological and molecular evidence confirmed HEV as the etiology. Mixing of contaminated drain water with the domestic water supply may have triggered this outbreak. Subsequent changing of the defaulted water pipelines and its segregation from drain pipelines by the health authorities resulted in progressive decline of this outbreak. Despite the limitations, periodic surveillance of HEV exposure pattern and reporting of small outbreaks would supplement to the global disease burden data of hepatitis E., (© 2020 Wiley Periodicals LLC.)

Hepatitis E virus (HEV) infection is considered a neglected disease of major concern in developed countries. Clinically, HEV occurs as an acute and self-limited disease, though chronic cases mostly associated to HEV-3 are now being commonly reported in immunocompromised individuals and solid organ transplant recipients. Transmission of HEV through blood and derivatives have been increasingly described in the last years, highlighting the importance of including this agent on the screening programs. Since 2010 both acute and chronic hepatitis E cases have been frequently reported in Uruguay. However, updated prevalence data among different population groups are lacking and HEV is not currently screened in blood banks. Herein, we report a seroprevalence and molecular survey of HEV in 400 plasma samples from blood donors. Overall, our results showed an HEV seroprevalence rate of 10% (40/400); almost 10-fold higher than 20 years ago. Total anti-HEV immunoglobulin antibodies were found to increase with age. Moreover, we reported an RNA detection rate of at least 0.75%, and two strains were sequenced. Phylogenetic analysis grouped them with human and swine HEV-3 strains from Uruguay. Data presented here should prompt public health policies of HEV screening in blood banks to minimize the risk of transfusion-transmitted hepatitis E., (© 2020 Wiley Periodicals LLC.)

Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.

The aim of this study was to assess the prevalence of hepatitis E virus (HEV) in a young population from the Northeast region of Argentina. Four hundred and twelve patients under 18 years old, from rural areas of Chaco Province, were tested for anti-HEV immunoglobulin G (IgG) using enzyme-linked immunosorbent assay. Anti-HEV IgG antibodies were detected in 7 out of 412 patients, accounting for an overall 1.7% prevalence. HEV infection in developing countries is associated to lack of clean drinking water. Consequently, the seroprevalence observed in children in rural areas of Chaco, Argentina, where the access to tap water is less than 15%, was unexpectedly low., (© 2020 Wiley Periodicals LLC.)

Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging public health infection which has an increasing incidence across Europe. Because of the apparent lack of species barriers, HEV was characterized as a zoonotic agent. Swine are recognized as the main reservoir, but HEV is also found in wild animals such as ungulates, lagomorphs, and bats. Our work aimed at detecting the HEV presence in wild fauna in two hunting areas of Northern Italy (Parma and Sondrio areas) with different environmental and anthropic characteristics to investigate its possible role as reservoir. Liver samples were collected from wild boars, red deer, roe deer and chamois, and viral identification was carried out by One-Step RT Real-time PCR. Positive samples were genotyped, and phylogenetic analysis was performed. The virus was found only in the wild boar population, with different prevalence and subtypes in the two areas (14% HEV3a and 1.2% close to HEV3f in Parma and Sondrio, respectively). Wild ruminants seem otherwise to pose a marginal risk. Given the high pig farm density in the Parma area, and expansion of the wild boar population, continuous monitoring of the strains circulating in wildlife is crucial.

People who use crack-cocaine (PWUCC) have numerous vulnerabilities and pose a challenge to health and social assistance services. The exposure to pathogens and risk situations occur differently according to each individual, region and social group. This study identified the presence, genotypes and factors associated with hepatitis E virus (HEV) exposure among a community-recruited cohort of 437 PWUCC in northern Brazil. Epidemiological information was collected through community-based assessments and interviews. Thereafter, blood and fecal samples were collected and tested for HEV using an immunoenzymatic assay, and the genotype was identified by PCR. Logistic regressions were used to identify the risk factors independently associated with exposure to HEV. In total, 79 (18.1%) PWUCC were exposed to HEV: 73 (16.7%) for IgG and six for IgG + IgM. HEV RNA was detected in six fecal samples and in two blood samples from PWUCC with IgM + IgG. Subtype 3c was identified in all of the samples. The factors associated with exposure to HEV were low monthly income, unstable housing (e.g., homelessness), crack-cocaine use ≥40 months, and the shared use of crack-cocaine equipment. The current study provides unique initial insights into HEV status and risk factors among PWUCC in a remote area in Brazil, with diverse implications for urgently improved diagnosis, prevention, and treatment intervention needs.

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. While the transmission in developing countries is dominated by fecal-oral route via drinking contaminated water, the zoonotic transmission is the major route of HEV infection in industrialized countries. The discovery of new HEV strains in a growing number of animal species poses a risk to zoonotic infection. However, the exact mechanism and the determinant factors of zoonotic infection are not completely understood. This review will discuss the current knowledge on the mechanism of cross-species transmission of HEV infection, including viral determinants, such as the open reading frames (ORFs), codon usage and adaptive evolution, as well as host determinants, such as host cellular factors and the host immune status, which possibly play pivotal roles during this event. The pathogenesis of hepatitis E infection will be briefly discussed, including the special forms of this disease, including extrahepatic manifestations, chronic infection, and fulminant hepatitis in pregnant women.

Hepatitis E virus (HEV) is the causative agent of acute and chronic hepatitis in humans. The zoonotic HEV genotype 3 is the main genotype in Europe. The foodborne transmission via consumption of meat and meat products prepared from infected pigs or wild boars is considered the major transmission route of this genotype. High hydrostatic pressure processing (HPP) is a technique, which can be used for inactivation of pathogens in food. Here, preparations of a cell culture-adapted HEV genotype 3 strain in phosphate-buffered saline (PBS) were subjected to HPP and the remaining infectivity was titrated in cell culture by counting fluorescent foci of replicating virus. A gradual decrease in infectivity was found by application of 100 to 600 MPa for 2 min. At 20 °C, infectivity reduction of 0.5 log 10 at 200 MPa and 1 log 10 at 400 MPa were observed. Slightly higher infectivity reduction of 1 log 10 at 200 MPa and 2 log 10 at 400 MPa were found by application of the pressure at 4 °C. At both temperatures, the virus was nearly completely inactivated (>3.5 log 10 infectivity decrease) at 600 MPa; however, low amounts of remaining infectious virus were observed in one of three replicates in both cases. Transmission electron microscopy showed disassembled and distorted particles in the preparations treated with 600 MPa. Time-course experiments at 400 MPa showed a continuous decline of infectivity from 30 s to 10 min, leading to a 2 log 10 infectivity decrease at 20 °C and to a 2.5 log 10 infectivity decrease at 4 °C for a 10 min pressure application each. Predictive models for inactivation of HEV by HPP were generated on the basis of the generated data. The results show that HPP treatment can reduce HEV infectivity, which is mainly dependent on pressure height and duration of the HPP treatment. Compared to other viruses, HEV appears to be relatively stable against HPP and high pressure/long time combinations have to be applied for significant reduction of infectivity., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Foodborne viruses have been recognized as a growing concern to the food industry and a serious public health problem. Hepatitis A virus (HAV) is responsible for the majority of viral outbreaks of food origin worldwide, while hepatitis E virus (HEV) has also been gaining prominence as a foodborne viral agent in the last years, due to its zoonotic transmission through the consumption of uncooked or undercooked infected meat or derivatives. However, there is a lack of scientific reports that gather all the updated information about HAV and HEV as foodborne viruses. A search of all scientific articles about HAV and HEV in food until March 2020 was carried out, using the keywords "HAV", "HEV", "foodborne", "outbreak" and "detection in food". Foodborne outbreaks due to HAV have been reported since 1956, mainly in the USA, and in Europe in recent years, where the number of outbreaks has been increasing throughout time, and nowadays it has become the continent with the highest foodborne HAV outbreak report. Investigation and detection of HAV in food is more recent, and the first detections were performed in the 1990s decade, most of them carried out on seafood, first, and frozen food, later. On the other hand, HEV has been mainly looked for and detected in food derived from reservoir animals, such as meat, sausages and pate of pigs and wild boars. For this virus, only isolated cases and small outbreaks of foodborne transmission have been recorded, most of them in industrialized countries, due to HEV genotype 3 or 4. Virus detection in food matrices requires special processing of the food matrix, followed by RNA detection by molecular techniques. For HAV, a real-time PCR has been agreed as the standard method for virus detection in food; in the case of HEV, a consensus assay for its detection in food has not been reached yet. Our investigation shows that there is still little data about HAV and HEV prevalence and frequency of contamination in food, prevalent viral strains, and sources of contamination, mainly in developing countries, where there is no research and legislation in this regard. Studies on these issues are needed to get a better understanding of foodborne viruses, their maintenance and their potential to cause diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong., Approach and Results: We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain., Conclusions: HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories., (© 2020 by the American Association for the Study of Liver Diseases.)

Hepatitis E virus (HEV) infection can cause acute and chronic hepatitis in humans. The zoonotic HEV genotype 3, which is highly prevalent in Europe, is mainly transmitted by consumption of raw meat and raw meat products produced from infected pigs or wild boars. High salt concentrations represent an important measure to preserve meat products and to inactivate foodborne pathogens. Here, an HEV preparation in phosphate-buffered saline (PBS) was subjected to different salt concentrations and the remaining infectivity was measured in a cell culture assay. Treatments with up to 20% sodium chloride for 24 h at 23 °C, with and without addition of 0.015% sodium nitrite or 0.03% sodium nitrate, did not lead to virus inactivation as compared to PBS only. Conditions usually applied for short-term and long-term fermented raw sausages were simulated by incubation at 22 °C for up to 6 days and at 16 °C for up to 8 weeks, respectively. Only 2% sodium chloride with 0.015% sodium nitrite showed a weak (< 1 log 10 ), but significant, infectivity reduction after 2 and 4 days as compared to PBS only. Addition of 2% sodium chloride and 0.03% sodium nitrate showed a slight, but not significant, decrease in infectivity after 2 and 8 weeks as compared to PBS only. In conclusion, HEV is highly stable at high salt concentrations and at salt conditions usually applied to preserve raw meat products.

Hepatitis E has emerged as a major transfusion-transmitted infectious risk. Two recipients of plasma from 2 lots (A and B) of pooled solvent/detergent-treated plasma were found to be infected by hepatitis E virus (HEV) that was determined to have been transmitted by the solvent/detergent-treated plasma. HEV RNA viral loads were 433 IU in lot A and 55 IU in lot B. Retrospective studies found that 100% (13/13) of evaluable lot A recipients versus 18% (3/17) of evaluable lot B recipients had been infected by HEV (p<0.001), albeit not necessarily at time of transfusion. Among evaluable recipients, 86% with a transfused HEV RNA load >50,000 IU were infected, most likely by the HEV-containing solvent/detergent-treated plasma, versus only 7% with a transfused HEV RNA load <50,000 IU (p<0.001). Overall, solvent/detergent-treated plasma might harbor HEV. Such an occurrence might result in a dose-dependent risk for transfusion-transmitted hepatitis E.

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. HEV causes high mortality in pregnant women. Its infection during pregnancy usually leads to fulminant hepatic failure, spontaneous abortions, premature delivery, or stillbirth. Vertical transmission of HEV has been reported, but the pathogenesis during pregnancy remains largely elusive. Pregnant rhesus macaques were infected with HEV to explore the pathogenesis of genotype 4 HEV infection during pregnancy. Active HEV infections were established with shedding viruses in the feces and blood, and elevated liver enzymes. Notably, higher viral titers and longer durations of HEV infection were found in HEV-infected pregnant rhesus macaques than in non-pregnant macaques. Premature delivery and fetal death occurred in one of the HEV-infected pregnant rhesus macaques. HEV RNA was detected in the liver, spleen, kidneys, and intestines of the dead fetus. This result strongly indicated vertical HEV transmission from mother to fetus. Maternal-transferred antibodies were observed in one of the babies with poor protection. The expressions of interferon-stimulated genes (ISGs) related to HEV infection were completely different between pregnant and non-pregnant rhesus macaques. During pregnancy, impaired innate immune responses, reduced progesterone levels, and shifts in immune states may aggravate HEV infection and result in adverse pregnancy outcomes.

Hepatitis E virus (HEV) (family Hepeviridae ) is one of the most common human pathogens, causing acute hepatitis and an increasingly recognized etiological agent in chronic hepatitis and extrahepatic manifestations. Recent studies reported that not only are the classical members of the species Orthohepevirus A (HEV-A) pathogenic to humans but a genetically highly divergent rat origin hepevirus (HEV-C1) in species Orthohepevirus C (HEV-C) is also able to cause zoonotic infection and symptomatic disease (hepatitis) in humans. This review summarizes the current knowledge of hepeviruses in rodents with special focus of rat origin HEV-C1. Cross-species transmission and genetic diversity of HEV-C1 and confirmation of HEV-C1 infections and symptomatic disease in humans re-opened the long-lasting and full of surprises story of HEV in human. This novel knowledge has a consequence to the epidemiology, clinical aspects, laboratory diagnosis, and prevention of HEV infection in humans.

To further investigate the prevalence of hepatitis E virus (HEV) infection and characterize HEV genomes among Japanese wild boars (Sus scrofa leucomystax), 1880 boars captured in 17 prefectures in Japan from 2013 to 2019 were studied. Overall, anti-HEV IgG was detected in 8.9 % and HEV RNA was detected in 3.9 % of boars, which was comparable with our previous studies during 2003-2013 (10.3 % and 3.5 %, respectively). Among 74 boar HEV strains obtained from infected boars in the present study, 50 (68 %) were classified into genotype 3 (3a and 3b), 23 (31 %) were classified into genotype 4 (4i), and the remaining strain (wbJGF&#95;19-1) was classified into genotype 5. The wbGF&#95;19-1 strain shared 92.7 % identity over the entire genome with the prototype genotype 5 strain (JBOAR135-Shiz09). The identification of the second genotype 5 HEV strain in a place that is located only 100 km from the site at which JBOAR135-Shiz09 was identified, suggests that genotype 5 HEV circulates within a relatively close range in Japan. Genetically similar HEV strains forming a clade were identified from wild boars living in each area during the observation period of 11-13 years, although the nucleotide sequence changed gradually, accounting for up to 3.4-3.6 % within the 412-nucleotide ORF2 sequence. Eight groups of boars with a cluster of HEV infections were observed, consisting of two, three or four infected offspring, presumably born to the same mother or offspring with their mother. These results suggest that wild boars continue to be important reservoirs for HEV infection in humans in Japan., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) infection is endemic in developed and developing countries. Although the seroprevalence of HEV among the Egyptians is high, the sources of HEV infection in Egypt are not completely identified. Zoonotic HEV transmission among Egyptians is underestimated. Recently, we detected HEV in the milk of cows, this suggests the possibility of HEV transmission through the ingestion of contaminated milk. However, the role of small ruminants especially the goats in HEV epidemiology in Egypt remains unclear. Herein, we screened HEV markers in the edible goat products, mainly the milk and liver and we assessed the risk factor for HEV infection to the goat owners. A total of 280 goat milk samples were collected from 15 villages in the Assiut governorate. Anti-HEV IgG and HEV Ag were detected in 7.14% and 1.8% of the samples, respectively. HEV RNA was detected in 2 milk samples, cladogram analysis revealed that the isolated viruses belonged to HEV-3 subtype 3a. One viral isolate showed high homology to HEV recently isolated from the cow milk in the same geographic area. The level of anti-HEV IgG and HEV Ag were comparable in the milk and matched blood samples. While the urine and stool of HEV seropositive goats tested negative for HEV markers. HEV RNA was also detectable in the fresh goat liver samples (n = 2) derived from HEV seropositive goats. Finally, we analyzed HEV seroprevalence in households (n = 5) that owned the seropositive goats and households (n = 5) that owned the seronegative goats. Interestingly, anti-HEV IgG was recorded in 80% of households owned and frequently consumed the products of HEV seropositive goats, while HEV markers were not detectable in the owners of the seronegative goats. In conclusion: Here, we report HEV in the milk and liver of goats distributed in the villages of Assiut governorate. Higher HEV seroprevalence was recorded in the households that owned the seropositive goats. Investigation of the goat products is pivotal to assess the risk factor of HEV transmission to villagers in the Assiut governorate., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) infection is both a major public health concern and emerging global health concern, with a documented incidence of 20 million, 3.4 million clinical cases, 70,000 deaths, and 3,000 stillbirths. The aetiologic agent, HEV is a primarily enterally transmitted hepatotropic virus. Fecal samples were collected from three selected pig farms across Ibadan, South-west Nigeria. Randomly picked samples were pooled per unit pen and fecal suspensions prepared were subjected to HEV Antigen (Ag) enzyme-linked immunosorbent assay. Molecular probing was done by Reverse Transcription and nested polymerase reaction (RT-nPCR) and deep sequencing. Sequencing was done paired-end for 300 cycles using the HiSeq system. Overall farm prevalence of 66.7% (2/3) and prevalence at individual level of 13.2% (9/68) were recorded. All nine samples positive for the ELISA screen were negative when subjected to RT-nPCR assays. Further, on deep sequencing, no HEV genomic fragment was found in the sample using de-novo assembly. Findings suggest possibly inapparent HEV in the pigs studied or a yet to be identified protein with HEV-Ag cross-reactivity ability on ELISA, thus constituting a possible risk of exposure to HEV infection in the population. Consequently, we recommend prompt intervention to unravel the mystery and break the chain of transmission.

Hepatitis E virus is a zoonotic pathogen for which pigs are recognized as the major reservoir in industrialised countries. A multiscale model was developed to assess the HEV transmission and persistence pattern in the pig production sector through an integrative approach taking into account within-farm dynamics and animal movements based on actual data. Within-farm dynamics included both demographic and epidemiological processes. Direct contact and environmental transmission routes were considered along with the possible co-infection with immunomodulating viruses (IMVs) known to modify HEV infection dynamics. Movements were limited to 3,017 herds forming the largest community on the swine commercial network in France and data from the national pig movement database were used to build the contact matrix. Between-herd transmission was modelled by coupling within-herd and network dynamics using the SimInf package. Different introduction scenarios were tested as well as a decrease in the prevalence of IMV-infected farms. After introduction of a single infected gilt, the model showed that the transmission pathway as well as the prevalence of HEV-infected pigs at slaughter age were affected by the type of the index farm, the health status of the population and the type of the infected farms. These outcomes could help design HEV control strategies at a territorial scale based on the assessment of the farms' and network's risk., Competing Interests: The authors have declared that no competing interests exist.

In recent decades, cases of autochthonous hepatitis E (HE) have sharply increased in European countries where foodborne transmission is considered the main route of HE virus (HEV) transmission. Although rabbits are considered the main reservoir of the zoonotic HEV-3ra subtype, information on the role of wild lagomorphs in the epidemiology of HEV remains scarce. The aim of this study therefore was to assess the circulation of HEV in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis), the most important lagomorph species in Spanish Mediterranean ecosystems. Liver samples from 372 wild rabbits and 78 Iberian hares were analysed using a broad-spectrum RT-PCR that detects HEV genotypes 1-8. None of the 450 lagomorphs tested were positive for HEV infection. To the best of our knowledge, this is the first study to assess HEV circulation in wild rabbits in Spain and the first to evaluate HEV infection in Iberian hares. Our results indicate absence of HEV circulation in wild rabbits and Iberian hares in southern Spain during the study period, which suggests that the risk of transmission of HEV from wild lagomorphs to other species, including humans, is low., (© 2020 Blackwell Verlag GmbH.)

While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.

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., (© 2020 Her Majesty the Queen in Right of Canada, Zoonoses and public Health published by Blackwell Verlag GmbH Reproduced with the permission of the Minister of Public Health Agency of Canada.)

Hepatitis E virus is a common cause of acute hepatitis and acute liver failure in resource-constrained parts of the world. The disease is particularly severe when the infection occurs during pregnancy. In developed countries, human infections occur primarily through zoonotic transmission from animal reservoirs; however, clinical disease is less frequent than in the developing world. The virus strains prevalent in these areas also cause chronic infection in immunocompromised persons, which, if untreated, can progress to cirrhosis; such infection responds well to oral ribavirin. A safe and highly effective recombinant vaccine is available in China, but is not available elsewhere., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels ( p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.

A 64-year-old woman was infected with hepatitis E virus (HEV) during chemotherapy for leukemia. By retrospective analyses of stored serum from the blood products and the patient, the source of the infection was determined to be platelet concentration (PC) transfused during chemotherapy. The partial nucleotide sequence of the HEV strain isolated from the donated PC and that from the patient's sera was identical and was subgenotype 3b. Clinical indicators such as alanine aminotransferase, HEV RNA titer, and anti-HEV antibodies in the serum were investigated from the beginning of the infection until 1 year after the termination of HEV infection. HEV RNA had propagated over 6 months and then cleared spontaneously after the completion of chemotherapy. Anti-HEV antibodies appeared in the serum just before the clearance of HEV RNA. Interestingly, HEV RNA was detected in the patient's urine, spinal fluid, and saliva. The HEV RNA titers in those samples were much lower than in the serum and feces. No renal, neurological, or salivary gland disorders appeared during the follow-up. We observed virological and biochemical progress and cure of transfusion-transmitted chronic hepatitis E in the patient despite an immunosuppressive status during and after chemotherapy against hematological malignancy.

Introduction: Transmission of hepatitis E virus (HEV) through transfusion has been reported from countries where genotype 3 virus is predominant. Data from countries with predominantly genotype 1 HEV, such as India, are limited. We studied the risk of HEV transmission following transfusion of blood or blood components in India., Methods: Adult patients undergoing cardiac surgery who received transfusion of blood or blood products in the peri-operative period and who lacked history of any transfusion or surgery in the preceding 1 year were studied. A pre-transfusion blood specimen was collected for IgG anti-HEV antibody test. For the participants who were seronegative for anti-HEV, follow up specimens were collected at every 2-3-month intervals for up to 6 months after surgery and were tested for IgM and IgG anti-HEV antibodies., Results: Of the 335 participants originally enrolled, 191 (57%) could be followed up. Of them, 103 (53.9%) were seropositive for HEV IgG at baseline and were excluded. Of the remaining 88 participants (age 42 ± 14.1 years; 55 [63%] male), none reported hepatitis-like illness during the follow up period of 81 ± 23 days. Also, none of these 88 participants was found to have seroconversion to anti-HEV IgM or IgG positivity in the follow up specimens., Conclusion: Transfusion-mediated transmission of HEV was not observed in our cohort and may be infrequent in the Indian population, where genotype 1 is the predominant HEV type.

Hepatitis E virus (HEV) infection is endemic in many developing countries and becomes of interest in the developed countries. Several animals are sources of HEV infection to humans. Recently, HEV was detected in the milk of cows in China, this data comes up with the probability of HEV transmission to humans via ingestion of contaminated milk. In Egypt, contaminated water and residing in rural communities are risk factors for HEV infection, while limited data is available on the zoonotic HEV transmission. Since pigs, wild boars, camels are not common in Egypt, we investigated if cows and/or cow milk represent a risk factor for HEV transmission in the Assiut governorate. Milk samples (n = 480), collected from Assiut city and 12 non-mixed dairy farms distributed in the rural communities, were tested for HEV markers such as anti-HEV IgG, HEV RNA, and HEV Ag. All milk samples collected from Assiut city (n = 220) were negative for HEV markers. Also, milk samples collected from 11 farms (n = 220) were negative for HEV markers. While, in one farm, we could detect anti-HEV IgG in 8 out of 40 samples (20%), HEV RNA and HEV Ag were detectable in 1 out of 40 samples (2.5%). However, we could not detect the HEV markers in the stool from anti-HEV IgG positive cows. Surprisingly, phylogenetic analysis of the isolated virus revealed it belonged to HEV-3 subtype 3a. Importantly, when cows from the positive farm were retested 1 month later, we observed an increase in the number of animals that were positive for anti-HEV IgG (10/40, 25%). In addition, the level of anti-HEV IgG was significantly higher in the milk of these cows in the second collection than the samples of the first collection suggesting ongoing infection on this farm. In conclusion: we reported that HEV-3 and/or HEV like agent was detected in the milk of the cow distributed in rural communities of Assiut governates. Investigation of the cow milk should be done to assess if the cow milk is a risk factor for HEV transmission for Egyptian people, especially in rural communities., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This review focuses on reports of hepatitis E virus, hantavirus, rotavirus, coronavirus, and arenavirus in synanthropic rodents (Rattus rattus, Rattus norvegicus, and Mus musculus) within urban environments. Despite their potential impact on human health, relatively few studies have addressed the monitoring of these viruses in rodents. Comprehensive control and preventive activities should include actions such as the elimination or reduction of rat and mouse populations, sanitary education, reduction of shelters for the animals, and restriction of the access of rodents to residences, water, and food supplies.

Hepatitis E virus (HEV) is a quasi-enveloped, positive-sense single stranded RNA virus. HEV continually expands the host ranges across animal species. In this study, the possibility of cross-species infection with swine HEV-3 was investigated using rabbits. A total of fourteen 8-week old, specific pathogen-free rabbits were divided into three experimental groups. Four rabbits were used as negative controls, four rabbits were infected with rabbit HEV as positive controls, and six rabbits were inoculated with swine HEV-3. HEV RNA were detected from serum and fecal samples after viral challenge. The levels of anti-HEV antibodies, pro-inflammatory cytokines (IL-1, IL-6, TNF-α and IFN-α), and liver enzymes (alanine and aspartate aminotransferases) were determined in serum samples. Histopathological lesions were examined in liver tissues. Viral RNA and anti-HEV antibodies were identified in rabbits inoculated with swine HEV-3 demonstrating positive infectivity of the virus. However, pro-inflammatory cytokine and liver enzyme levels in serum were not significantly elevated, and only mild inflammatory lesions were detected in the liver tissues of rabbits infected with swine HEV-3. These results suggest that swine HEV-3 can engage in cross-species transmission to rabbits, but causes only mild inflammation of the liver., Competing Interests: The authors declare no conflict of interest.