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BackgroundHepatitis-E virus (HEV), an etiologic agent of acute inflammatory liver disease, is a significant cause of morbidity and mortality in South Asia. HEV is considered endemic in Nepal; but data on population-level infection transmission is sparse.MethodsWe conducted a longitudinal serosurvey in central Nepal to assess HEV exposure. At each visit, capillary blood samples were collected and analyzed for the presence of anti-HEV IgG antibodies. The study took place between February 2019 and April 2021, with up to 4 visits per participant approximately 6 months apart.ResultsWe collected 2513 samples from 923 participants aged 0-25 years, finding a seroprevalence of 4.8% and a seroincidence rate of 10.9 per 1000 person-years. Young adults and individuals consuming surface water faced the highest incidence of infection. Geospatial analysis identified potential HEV clusters, suggesting a need for targeted interventions.SignificanceOur findings demonstrate that HEV is endemic in Nepal and that the risk of infection increases with age.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications. It's poorly understood how renal manifestations develop in HEV infection in patients. Here, the authors observe glomerular accumulation of the viral protein ORF2 in complex with host IgG in immunocompromised patients with chronic or acute HEV infection who developed glomerulonephritis. [ABSTRACT FROM AUTHOR]

ABSTRACT Acute hepatitis E virus infection is a serious global health problem, which a significant cause of morbidity and mortality. The aim of the present study was to characterise the clinical features and therapeutic response of patients with acute HEV infection and identify risk factors for poor prognosis. In a retrospective study from 01 January 2014 to 01 Januray 2022, we collected baseline data from all patients eligible for acute hepatitis E virus (HEV) infection and followed up with all patients via interviews and medical records. We explored the clinical feature of Chinese patients with acute HEV infection. The follow‐up data of patients were used to identify risk factors for poor prognosis. In total, 628 acute hepatitis E (AHE) patients fulfilled the inclusion criteria and did not meet the exclusion criteria. Among them, 452 were males and 176 were females (M:F = 2.57:1). The median age at diagnosis was 57.0 years (interquartile range: 46–64 years). The median baseline serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were elevated in this cohort (642.3 U/L, 216.2 U/L, 104.1 μmol/L, respectively). The median hospitalisation duration was 16 days. Compared with patients without other liver diseases, patients with liver cirrhosis show lower baseline ALT and AST level, poorer coagulation indices and higher MELD scores. According to multivariate analysis, liver cirrhosis, high MELD score, low albumin concentration was found to be independent predictors of poor prognosis in patients with AHE. Our study used a lager sample size to validate that some demographic and serological features were quite different between patients with/without CLDs. Liver cirrhosis was a significant independent predictor of poor prognosis in acute HEV hepatitis. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown.This was a multicentre, prospective, observational, matched case–control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein–Barr virus, cytomegalovirus, parvovirus B19, varicella‐zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection.Fifty‐seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43).Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis. [ABSTRACT FROM AUTHOR]

Aim: This study investigated hepatitis E virus (HEV) prevalence among pregnant women in Siem Reap, Cambodia, by developing a cost‐effective, user‐friendly in‐house enzyme‐linked immunosorbent assay (ELISA) for detecting total anti‐HEV immunoglobulins (Ig). Methods: The in‐house ELISA was designed for large‐scale screening in resource‐limited settings. Its performance was benchmarked against two commercial tests: the Anti‐HEV IgG EIA (Institute of Immunology, Co. Ltd) and the Anti‐HEV IgG RecomLine LIA (Mikrogen). The in‐house ELISA demonstrated a sensitivity of 76% and 71.4%, and a specificity of 94.1% and 98.6%, against the two commercial tests, respectively, with overall agreement rates of 92.4% and 94.3%. Results: Among 1565 tested pregnant women, 11.6% were anti‐HEV positive. Prevalence increased with age, particularly in women aged 35–40 years and over 40 years. No significant associations were found with education, number of children, family size, or history of blood transfusion and surgery, except for the occupation of the family head as a public officer. Of the total anti‐HEV positive women, 22.7% had anti‐HEV IgM, indicating recent or ongoing infection. Conclusion: The study concluded that the in‐house ELISA is a viable option for HEV screening in regions with limited resources due to its high accuracy and cost‐effectiveness. It is particularly suitable for large‐scale studies and public health interventions in areas where HEV is endemic and poses a significant risk to pregnant women. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically transmitted hepatitis. HEV infects various mammalian hosts and belongs to the genus Paslahepevirus in the family Hepeviridae. While swine are recognized as the main hosts of HEV, rabbits, which can also be affected by swine HEV-3 related strains, serve as the primary reservoir for the distinct emerging and zoonotic HEV-3ra subtype. In Portugal, where the European wild rabbit is abundant, their role in HEV epidemiology remains unclear. The primary aim of the present research was to evaluate the circulation and the potential for HEV infection within these species. This study employed a molecular and longitudinal serological approach to investigate HEV in Portuguese rabbits. Among the 205 wild rabbits tested, a seroprevalence of 2.44% (95% CI: 0.80–5.60) was found, with no significant associations with age, sex, localization, or sampling dates. Seropositive animals were found in the south and center regions of the country. HEV RNA was not detected in 120 fecal samples, suggesting a natural, low level, and widespread viral circulation. The study underscores the need for further research to comprehend HEV dynamics in these species, which is crucial for assessing potential transmission risks to humans. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is an important emerging pathogen producing significant morbidity in immunosuppressed patients. HEV has been detrimental to solid organ transplant (SOT) patients, cancer patients, and HIV-positive patients, where chronic HEV infections occur. Blood-borne transfusions and multiple cases of chronic HEV infection in transplant patients have been reported in the past few decades, necessitating research on HEV pathogenesis using immunosuppressed animal models. Numerous animal species with unique naturally occurring HEV strains have been found, several of which have the potential to spread to humans and to serve as pathogenesis models. Host immunosuppression leads to viral persistence and chronic HEV infection allows for genetic adaptation to the human host creating new strains with worse disease outcomes. Procedures necessary for SOT often entail blood transfusions placing immunosuppressive patients into a "high risk group" for HEV infection. This scenario requires an appropriate immunosuppressive animal model to understand disease patterns in these patients. Hence, this article reviews the recent advances in the immunosuppressed animal models for chronic HEV infection with emphasis on pathogenesis, immune correlates, and the liver pathology associated with the chronic HEV infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hepatitis E virus (HEV) is an RNA virus recognized to be spread mainly by fecal-contaminated water. Its infection is known to be a serious threat to public health globally, mostly in developing countries, in which Africa is one of the regions sternly affected. An African-based vaccine is necessary to actively prevent HEV infection. Methods: This study developed an in silico epitope-based subunit vaccine, incorporating CTL, HTL, and BL epitopes with suitable linkers and adjuvants. Results: The in silico-designed vaccine construct proved immunogenic, non-allergenic, and non-toxic and displayed appropriate physicochemical properties with high solubility. The 3D structure was modeled and subjected to protein docking with Toll-like receptors 2, 3, 4, 6, 8, and 9, which showed a stable binding efficacy, and the dynamics simulation indicated steady interaction. Furthermore, the immune simulation predicted that the designed vaccine would instigate immune responses when administered to humans. Lastly, using a codon adaptation for the E. coli K12 bacterium produced optimum GC content and a high CAI value, which was followed by in silico integration into a pET28 b (+) cloning vector. Conclusions: Generally, these results propose that the design of an epitope-based subunit vaccine can function as an outstanding preventive vaccine candidate against HEV, although validation techniques via in vitro and in vivo approaches are required to justify this statement. [ABSTRACT FROM AUTHOR]

The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7–95.3%), as assessed by bioanalyzer, with yields of 13.9–89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) poses a significant global health threat, with an estimated 20 million infections occurring annually. Despite being a self-limiting illness, in most cases, HEV infection can lead to severe outcomes, particularly in pregnant women and individuals with pre-existing liver disease. In the absence of specific antiviral treatments, the exploration of RNAi interference (RNAi) as a targeted strategy provides valuable insights for urgently needed therapeutic interventions against Hepatitis E. We designed small interfering RNAs (siRNAs) against HEV, which target the helicase domain and the open reading frame 3 (ORF3). These target regions will reduce the risk of viral escape through mutations, as they belong to the most conserved regions in the HEV genome. The siRNAs targeting the ORF3 efficiently inhibited viral replication in A549 cells after HEV infection. Importantly, the siRNA was also highly effective at inhibiting HEV in the persistently infected A549 cell line, which provides a suitable model for chronic infection in patients. Furthermore, we showed that a 5′ triphosphate modification on the siRNA sense strand activates the RIG-I receptor, a cytoplasmic pattern recognition receptor that recognizes viral RNA. Upon activation, RIG-I triggers a signaling cascade, effectively suppressing HEV replication. This dual-action strategy, combining the activation of the adaptive immune response and the inherent RNAi pathway, inhibits HEV replication successfully and may lead to the development of new therapies. [ABSTRACT FROM AUTHOR]

Human enteric viruses, such as hepatitis A virus (HAV), hepatitis E virus (HEV), and norovirus genogroups I and II (NoVGI and NoVGII), cause infections, and it has been largely demonstrated that mussels play an important role if consumed as raw or undercooked food matrices. This study aimed to investigate, through qualitative and quantitative biomolecular assays, the detection of partial genomic regions belonging to the most relevant enteropathogenic viruses for humans (HAV, HEV, NoVGI and NoVGII) in mussels (Mytilus galloprovincialis) farmed along the coasts of two Italian regions on the central Adriatic Sea: Abruzzo (Casalbordino, Chieti) and Molise (Termoli, Campobasso). A total of 425 animals were sampled, and the respective georeferentiations were registered. A total of 85 pools, each composed of five subjects/aliquots, were formed (22 from Abruzzo and 63 from Molise regions). This step was followed by homogenization and RNA extraction, and then the biomolecular assays [nested reverse transcription polymerase chain reaction (PCR) and real-time reverse transcription-quantitative PCR] were performed. 1.17% of the pool was positive for HAV RNA detection (10² copies/mL), 9.41% for HEV (10²-10³ copies/µL), 2.35% for NoVGI (10¹ copies/µL), and no pool was positive for NoVGII. This study demonstrated the human enteric viruses' presence in mussels farmed in a low-investigated marine area. Based on a one-health point of view, this paper aims to enforce the importance of biomolecular and epidemiological screenings as surveillance systems to guarantee human, animal, and environmental health. [ABSTRACT FROM AUTHOR]

Hepatitis E virus is a primary cause of acute hepatitis worldwide. The present study attempts to assess the genetic variability and evolutionary divergence among HEV genotypes. A vaccine promising capsid‐protein coding ORF‐2 gene sequences of HEV was evaluated using phylogenetics, model‐based population genetic methods and principal component analysis. The analyses unveiled nine distinct clusters as subpopulations for six HEV genotypes. HEV‐3 genotype samples stratified into four different subgroups, while HEV‐4 stratified into three additional subclusters. Rabbit‐infectious HEV‐3ra samples constitute a distinct cluster. Pairwise analysis identified marked genetic distinction of HEV‐4c and HEV‐4i subgenotypes compared to other genotypes. Numerous admixed, inter and intragenotype recombinant strains were detected. The MEME method identified several ORF‐2 codon sites under positive selection. Some selection signatures lead to amino acid substitutions within ORF‐2, resulting in altered physicochemical features. Moreover, a pattern of host‐specific adaptive signatures was identified among HEV genotypes. The analyses conclusively depict that recombination and episodic positive selection events have shaped the observed genetic diversity among different HEV genotypes. The significant genetic diversity and stratification of HEV‐3 and HEV‐4 genotypes into subgroups, as identified in the current study, are noteworthy and may have implications for the efficacy of anti‐HEV vaccines. [ABSTRACT FROM AUTHOR]

HEV antibody detection constitutes the main screening test for HEV infection. The aim of this study is to compare the sensitivity and specificity of four techniques: LIAISON® MUREX DiaSorin anti-HEV IgG and anti-HEV IgM assays, Hepatitis E VIRCLIA® IgM and IgG monotests, WANTAI HEV-IgM and IgG ELISA and VIDAS® anti-HEV IgM and IgG tests in five panels of samples configurated according to the immunoblot (RecomLine, Mikrogen, Neuss, Germany). Anti-HEV IgM sensitivity in the acute phase was 100% in all techniques, while sensitivity, including the immediate convalescence phase, was 96.74% for LIAISON®, 83.14% for VIRCLIA®, 84.78% for WANTAI and 88.04% for VIDAS®. Anti-HEV IgM specificity was 100% for both LIAISON® and VIRCLIA®. Anti-HEV IgM WANTAI agreed with VIRCLIA® with a good Kappa coefficient (κ = 0.71). Anti-HEV IgG post-infection sensitivity was 100% for LIAISON®, VIDAS® and VIRCLIA® and 99% for WANTAI. Anti-HEV IgG specificity reached 97.17% for LIAISON and 88.68% for VIRCLIA®. Our results demonstrated a better capacity of LIAISON® MUREX anti-HEV IgM than that of competitors for detecting acute infections as well as accurate anti-HEV IgG results and in how to resolve them. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and Hepatitis E virus (HEV) are zoonotic pathogens posing significant health concerns in rural Amazonia, a region marked by high endemicity, poverty, and limited healthcare access. However, the epidemiology of HBV and HEV in this ecosystem remains underexplored. This study examines the circulation of HBV and HEV at the human–wildlife interface and identifies risk factors within an isolated Amazonian indigenous community reliant on hunting for subsistence. Antibodies against HBV core antigens (HBcAbs) were found in three wildlife species: Cuniculus paca (0.8%), Tayassu pecari (1.6%), and Mazama americana (4.1%), marking the first record of HBV antibodies in free-ranging wildlife in the Amazon. However, further research is necessary to identify circulating strains and their relation to human HBV. HBcAbs were also detected in 9.1% of human samples, confirming exposure to HBV in the region. HEV IgG antibodies were present in 17.1% of humans and were associated with higher age. All wildlife and domestic animal samples tested negative for HEV, but transmission through consumption of wild animals and contaminated water needs further investigation. The identified risk factors highlight the urgent need for measures to promote safer food handling, improved sanitation, hygiene, and practices related to contact with wild animals. [ABSTRACT FROM AUTHOR]

This article discusses the detection of blood-borne pathogens in clotting factor concentrates from the 1970s and 1980s. The study found that concentrated coagulation factors derived from human blood donations during this time period were contaminated with viruses such as HIV-1 and hepatitis C. The authors used qPCR assays to test the clotting factor samples for various viruses and found that HCV, B19V, and HPgV-1 were the most frequently detected viruses. The study highlights the need for continued screening of blood products and the development of safer clotting products. [Extracted from the article]

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Background: HEV is endemic in several Middle Eastern countries including Saudi Arabia, which hosts the annual pilgrimage for Muslims from around the world. One of the Hajj rituals is the sacrifice of animals, including camels, cows, goats, and sheep. HEV Zoonosis is established in swine and other suspected species, including deer, rabbits, dromedary, and Bactrian camels. HEV was identified in small, domesticized animals like goats, cows, sheep, and horses. We previously investigated HEV seroprevalence in Camels. This study aimed to evaluate HEV seroprevalence in other highly consumed ruminants in Saudi Arabia, namely cows, sheep, and goats. Methods: Sera from cows (n = 47), goats (n = 56), and sheep (n = 67) were analyzed for the presence of HEV-IgG by using in-house developed ELISA assays. Results: The highest seroprevalence was found in sheep (62.7%), followed by cows (38.3%), and then goats (14.3%), with a p-value of < 0.001. No other demographic characteristics of the animals were significantly correlated with the HEV seroprevalence. Conclusions: This study provides baseline data as the first study on the seroprevalence of HEV in ruminant animals in Saudi Arabia. The high seroprevalence found in sheep and cows must be further investigated for the potential zoonotic HEV transmission to humans. Further studies are needed to investigate the active viremia in these animal species through nucleic acid detection and sequencing to provide data on the circulating HEV genotypes among the targeted animal species. The detection of HEV in different animal products, such as milk, liver, and others, also remains an important study area to consider. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV‐related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)‐negative HBV‐related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. Methods: This historical cohort study involved 1232 NA‐treated HBeAg‐negative patients who underwent curative hepatectomy for HBV‐related HCC from 2014 to 2019. The recurrence‐free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. Results: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348–3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537–4.942, p < 0.001 after PSM) in HBsAg‐negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg‐negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). Conclusions: These findings demonstrate the potential for HBeAg‐negative HBV‐related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis E virus (HEV) is a foodborne zoonotic pathogen that is supposed to be one of the most common causes of acute viral hepatitis. However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood–brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV‐induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase‐1, IL‐1β and IL‐18 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus‐like particles range from 30 to 40 nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase‐1, IL‐1β and IL‐18 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE‐cadherin degradation. The findings provide new insights into HEV‐associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV‐induced neurological disorder. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis E virus (HEV) is typically asymptomatic in developed countries but can be more severe in certain populations. We aim to describe the epidemiology of HEV‐associated hospitalisations from 1998 to 2020 in the United States, investigate risk factors for inpatient mortality and describe outcomes in pregnant women. We utilised the National Inpatient Sample and extracted cases of HEV‐associated hospitalisations using ICD‐9/10 diagnostic codes. Demographic, clinical and pregnancy data were extracted and analysed by chi‐square and logistic regression. We identified 3354 cases of HEV‐associated hospitalisations; 1689 (50.4%) were female and 1425 (42.5%) were non‐Hispanic White. The median age was 50 (IQR: 37–59) years. Hospitalisation rates for HEV ranged from 2.5 per 10,000,000 in 2008 to a peak of 9.6 per 10,000,000 people in the general U.S. population in 2004. The mortality rate was 5.2%. Age ≥ 40 years (OR: 7.73; 95% CI: 1.57–38.09; p = 0.012), HIV infection (OR: 4.63; 95% CI: 1.26–16.97; p = 0.021), and coagulopathy (OR: 7.22; 95% CI: 2.81–18.57; p < 0.001) were associated with increased odds of mortality within the HEV cohort. There were 226 pregnant women with HEV. Rates of maternal death, stillbirth and preterm birth were similar between HEV and non‐HEV pregnant cohorts. Hepatitis B and hepatitis C co‐infection were significantly more common in the HEV pregnant cohort (p < 0.05). HEV‐associated hospitalisations are uncommon in the United States, but likely underdiagnosed. Certain risk factors can be used to predict prognosis of these hospitalised patients. Pregnant women with HEV appear to have favourable maternal and fetal outcomes despite hepatitis B and C co‐infection. [ABSTRACT FROM AUTHOR]

Consumption of raw or undercooked wild boar (WB) meat is considered an important risk factor for hepatitis E virus (HEV) infection in humans. The possibility of HEV contamination during the slaughtering practices may pose an additional risk. Based on these assumptions, we evaluated HEV contamination of WB meat hunted in Umbria (central Italy) during the 2022–2023 hunting season by real-time RT-PCR. Herein, we show that 10.8% of livers from slaughtered WB were positive for HEV RNA, thus providing an estimate of HEV infection in WB in the Umbria region. Then, by evaluating paired liver–muscle samples from both HEV-positive and HEV-negative animals, we found evidence of muscle HEV contamination in 33% and 14% of cases, respectively. This is the first report on the detection of HEV in WB meat in Umbria, an Italian region with diffuse WB hunting and consumption. The evidence of contamination provided by our study underscores the importance of adopting good hygienic practices in the processing stages of hunted WB carcasses to significantly reduce meat contamination and the risk posed for the final consumer. [ABSTRACT FROM AUTHOR]

Although the Hepatitis E virus (HEV) is an emerging global health burden, little is known about its interaction with the host cell. HEV genome encodes three proteins including the ORF2 capsid protein that is produced in different forms, the ORF2i protein which is the structural component of viral particles, and the ORF2g/c proteins which are massively secreted but are not associated with infectious material. We recently demonstrated that the endocytic recycling compartment (ERC) is hijacked by HEV to serve as a viral factory. However, host determinants involved in the subcellular shuttling of viral proteins to viral factories are unknown. Here, we demonstrate that the AP-1 adaptor complex plays a pivotal role in the targeting of ORF2i protein to viral factories. This complex belongs to the family of adaptor proteins that are involved in vesicular transport between the trans-Golgi network and early/recycling endosomes. An interplay between the AP-1 complex and viral protein(s) has been described for several viral lifecycles. In the present study, we demonstrated that the ORF2i protein colocalizes and interacts with the AP-1 adaptor complex in HEV-producing or infected cells. We showed that silencing or drug-inhibition of the AP-1 complex prevents ORF2i protein localization in viral factories and reduces viral production in hepatocytes. Modeling of the ORF2i/AP-1 complex also revealed that the S domain of ORF2i likely interacts with the σ1 subunit of AP-1 complex. Hence, our study identified for the first time a host factor involved in addressing HEV proteins (i.e. ORF2i protein) to viral factories. [ABSTRACT FROM AUTHOR]

Background: The hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously. Case description: A 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient's neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient's neurological status improved after the administration of intravenous immunoglobulins. Conclusion: This case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although pets provide several social-emotional benefits for children, the risk of zoonosis must be considered among immunocompromised individuals. Methods: A prospective study was conducted in a tertiary hospital including immunocompromised patients younger than 20 years owning dogs and/or cats. Colonization and/or infection was evaluated by stool studies, bacterial swabs, blood polymerase chain reaction and serological studies in both patients and their pets, to evaluate potential zoonotic transmission occurrence. Results: We included 74 patients and their 92 pets (63 dogs, 29 cats). Up to 44.6% of the patients and 31.5% of the pets had at least 1 positive result. Up to 18.4% of pets' fecal samples were positive (bacteria, parasites or hepatitis E virus). No helminths were observed despite the high frequency of incorrect intestinal deworming practices. Among children, gastrointestinal microorganisms were found in 37.3% (primarily Clostridium difficile). Colonization by Staphylococcus pseudintermedius was common among pets (8.0%) but not among children (0.0%). No shared colonization between owners and pets was observed, except in one case (Blastocystis in both patient and pet feces). Among patients, serologies were positive for Strongyloides stercoralis (14.8%), Toxocara canis (3.2%), Bartonella henselae (19.1%) and hepatitis E (5.6%). Serology was positive for Rickettsia spp. (22.6%) and Babesia spp. (6.5%) in dogs and for Leishmania spp. (14.3%) and Toxoplasma spp. (14.3%) in cats. Conclusion: Exposure to zoonotic agents was detected in both patients and pets; however, shared colonization events were almost nonexistent. In our cohort, dogs and cats do not appear to entail high zoonosis transmission risk for immunocompromised patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis E virus (HEV) infection formerly and predominantly occurred in rural areas. However, it has recently been spread to urban and peri-urban areas. This study aimed to estimate the seroprevalence of HEV in pigs collected from urban and rural areas in Bali. The potential of the pig farmers' risk level for being exposed to HEV and the virus transmitted to them in association with their pig-rearing practices was also assessed. Materials and Methods: A total of 183 pigs from 68 herds were sampled in this study, with 91 pigs collected from Denpasar as the representative samples of urban areas and 92 pigs from Karangasem Regency as the representative samples from rural areas. Sera from the sampled pigs were collected and immunoglobulin G antibodies against HEV were detected using a commercial enzyme-linked immunosorbent assay. A questionnaire was prepared for interviewing the farmers. Bivariable and multivariable logistic regression analyses were performed to identify the putative factors associated with seropositivity. Meanwhile, the potential risk-incurring practices of the farmers for HEV being transmitted to them from their pig-rearing practices were assessed by scoring their responses from the interview. Results: Overall, 23.5% (43/183) (95% confidence interval [CI]: 17.6-30.3) pig sera tested were detected to have the antibodies against HEV. Among 68 pig herds, 36.8% (25) (95% CI: 25.4-49.3) of them had antibodies in at least one pig sampled from each herd. Pigs sampled from Karangasem were 5 times (Odds ratio [OR] 5.34, 95% CI: 2.27-13.54, p < 0.001) more likely to be seropositive than pigs collected from Denpasar. However, no difference was found in the seropositivity to HEV in pig herds between Denpasar and Karangasem (p = 0.05). In assessing the pig rearing management factors, pig farmers from Denpasar were 3 times (OR 3.0, 95% CI: 1.07-8.52, p = 0.05) more likely to rear pigs for economic investment compared to the farmers from Karangasem. Regarding anticipating pig diseases that can be transmitted to humans, farmers from Denpasar were 6 times (OR 5.72, 95% CI: 1.48-26.7, p = 0.0074) more likely to anticipate zoonotic diseases compared to the farmers from Karangasem. Similarly, pig farmers from Denpasar were 3 times (OR 3.29, 95% CI: 1.08-10.23, p = 0.035) more likely to anticipate pig diseases that could be transmitted to humans than the farmers from Karangasem. Pig farmers from Denpasar had 4 times the odds (OR 4.49, 95% CI: 1.11-18.19, p = 0.03) of washing their hands after going to the pigpens compared to the farmers from Karangasem. All the participants were categorized as being at high risk of HEV exposure and transmission. Conclusion: IgG antibodies against HEV were detected among pigs reared in rural areas of Karangasem and those reared in urban areas of Denpasar. This suggests that the risk of HEV exposure and transmission in these areas is not negligible. To minimize the risk, public education on zoonotic diseases, including HEV infection, transmission, and prevention, needs to be implemented and particularly targeted to local pig farmers. [ABSTRACT FROM AUTHOR]

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti‐HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post‐transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a foodborne virus transmitted through the faecal–oral route that causes viral hepatitis in humans worldwide. Ever since its discovery as a zoonotic agent, HEV was isolated from several species with an expanding range of hosts. HEV possesses several features of other RNA viruses but also has certain HEV‐specific traits that make its viral–host interactions inimitable. HEV leads to severe morbidity and mortality in immunocompromised people and pregnant women across the world. The situation in underdeveloped countries is even more alarming. Even after creating a menace across the world, we still lack an effective vaccine against HEV. Till date, there is only one licensed vaccine for HEV available only in China. The development of an anti‐HEV vaccine that can reduce HEV‐induced morbidity and mortality is required. Live attenuated and killed vaccines against HEV are not accessible due to the lack of a tolerant cell culture system, slow viral replication kinetics and varying growth conditions. Thus, the main focus for anti‐HEV vaccine development is now on the molecular approaches. In the current study, we have designed a multi‐epitope vaccine against HEV through a reverse vaccinology approach. For the first time, we have used viral ORF3, capsid protein and polyprotein altogether for epitope prediction. These are crucial for viral replication and persistence and are major vaccine targets against HEV. The proposed in silico vaccine construct comprises of highly immunogenic and antigenic T‐cell and B‐cell epitopes of HEV proteins. The construct is capable of inducing an effective and long‐lasting host immune response as evident from the simulation results. In addition, the construct is stable, non‐allergic and antigenic for the host. Altogether, our findings suggest that the in silico vaccine construct may be useful as a vaccine candidate for preventing HEV infections. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) is transmitted by the fecal route, usually through contaminated water in humans and/or infected animals, especially pigs. The objective of this study was to evaluate the level of anti-HEV antibodies in a panel of pig sera and to identify HEV in pig feces in farms. Methodology: The presence of HEV antibodies was tested by an in-house ELISA and a commercial ELISA IDvet. HEV genome was assessed by nested RT-PCR, and then, genotype was identified by sequencing (MinION Nanopore technology). Results: In 2017–2019, the 43% seroprevalence found in Forest Guinea was significantly higher than the 7% found in the Lower region (p < 0.01). Presence of HEV genotype 3c was demonstrated during a secondary study in the Lower region (Conakry) in 2022. Conclusion: The presence of HEV-3c in pigs calls for an evaluation of seroprevalence in human populations and for a HEV genotype human circulation check. Contribution Heading: This study is the first report, to our knowledge, of seroprevalence and characterization of HEV infection in pigs in Guinea. [ABSTRACT FROM AUTHOR]

The present study investigated the seropositivity rate of Hepatitis E virus (HEV) in domestic and working animals in Namibia, which included dogs, cats, horses, and donkeys. HEV poses a growing threat as a significant cause of human hepatitis globally and has several genotypes of varying zoonotic potential. As epidemiological data on the seroprevalence of HEV in Namibia is scarce, a serosurvey was conducted on archived serum samples of 374 dogs, 238 cats, 98 horses, and 60 donkeys collected between 2018 and 2022 from different regions, to assess the potential of these animals as sources of HEV infection. The findings revealed that 10.43% (n = 39/374) canine and 5.88% (n = 14/238) feline samples tested positive for HEV antibodies, whereas no seropositivity was detected in horses and donkeys. The study further examined the risk factors associated with HEV seropositivity, including animal sex, age, and geographical region, and noted a higher prevalence in dogs living in areas with intensive pig farming. Although there is no direct evidence indicating that these animals served as major reservoirs for HEV transmission to humans, the study underscores the importance of preventive measures to minimize contact exposure with pets considering the potential zoonotic risk, especially for susceptible risk groups. Further research is needed to explore the zoonotic potential of domestic animals and the epidemiological links between animal and human HEV transmissions in Namibia. [ABSTRACT FROM AUTHOR]

Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. The transmission route of rat-HEV is unidentified and requires further investigation. The HEV strains of the Paslahepevirus balayani species, belonging to the same Hepeviridae family, and including the zoonotic genotype HEV-3 usually found in pigs, have also sporadically been identified in rats. We sampled 115 rats (liver, lung, feces) between 2020 and 2023 in Northeast Italy and the HEV detection was carried out by using Reverse Transcription PCR. HEV RNA was detected in 3/115 (2.6%) rats who tested positive for HEV-C1 strains in paired lung, intestinal contents and liver samples. Overall, none tested positive for the Paslahepevirus balayani strains. In conclusion, our results confirm the presence of HEV-rat in Italy with a prevalence similar to previous studies but show that there is a wide heterogeneity of strains in circulation. The detection of HEV-C1 genotype of Rocahepevirus ratti species in some human cases of acute hepatitis suggests that HEV-C1 may be an underestimated source of human infections. This finding, with the geographically widespread detection of HEV-C1 in rats, raises questions about the role of rats as hosts for both HEV-C1 and HEV-3 and the possibility of zoonotic transmission. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis E virus (HEV) infection formerly and predominantly occurred in rural areas. However, it has recently been spread to urban and peri-urban areas. This study aimed to estimate the seroprevalence of HEV in pigs collected from urban and rural areas in Bali. The potential of the pig farmers’ risk level for being exposed to HEV and the virus transmitted to them in association with their pig-rearing practices was also assessed. Materials and Methods: A total of 183 pigs from 68 herds were sampled in this study, with 91 pigs collected from Denpasar as the representative samples of urban areas and 92 pigs from Karangasem Regency as the representative samples from rural areas. Sera from the sampled pigs were collected and immunoglobulin G antibodies against HEV were detected using a commercial enzyme-linked immunosorbent assay. A questionnaire was prepared for interviewing the farmers. Bivariable and multivariable logistic regression analyses were performed to identify the putative factors associated with seropositivity. Meanwhile, the potential risk-incurring practices of the farmers for HEV being transmitted to them from their pig-rearing practices were assessed by scoring their responses from the interview. Results: Overall, 23.5% (43/183) (95% confidence interval [CI]: 17.6–30.3) pig sera tested were detected to have the antibodies against HEV. Among 68 pig herds, 36.8% (25) (95% CI: 25.4–49.3) of them had antibodies in at least one pig sampled from each herd. Pigs sampled from Karangasem were 5 times (Odds ratio [OR] 5.34, 95% CI: 2.27–13.54, p < 0.001) more likely to be seropositive than pigs collected from Denpasar. However, no difference was found in the seropositivity to HEV in pig herds between Denpasar and Karangasem (p = 0.05). In assessing the pig rearing management factors, pig farmers from Denpasar were 3 times (OR 3.0, 95% CI: 1.07–8.52, p = 0.05) more likely to rear pigs for economic investment compared to the farmers from Karangasem. Regarding anticipating pig diseases that can be transmitted to humans, farmers from Denpasar were 6 times (OR 5.72, 95% CI: 1.48–26.7, p = 0.0074) more likely to anticipate zoonotic diseases compared to the farmers from Karangasem. Similarly, pig farmers from Denpasar were 3 times (OR 3.29, 95% CI: 1.08–10.23, p = 0.035) more likely to anticipate pig diseases that could be transmitted to humans than the farmers from Karangasem. Pig farmers from Denpasar had 4 times the odds (OR 4.49, 95% CI: 1.11–18.19, p = 0.03) of washing their hands after going to the pigpens compared to the farmers from Karangasem. All the participants were categorized as being at high risk of HEV exposure and transmission. Conclusion: IgG antibodies against HEV were detected among pigs reared in rural areas of Karangasem and those reared in urban areas of Denpasar. This suggests that the risk of HEV exposure and transmission in these areas is not negligible. To minimize the risk, public education on zoonotic diseases, including HEV infection, transmission, and prevention, needs to be implemented and particularly targeted to local pig farmers.

Aims: Hepatitis E caused by the hepatitis E virus (HEV) is prevalent worldwide. In China, considerable shifts in the epidemiology of hepatitis E have been observed over the last two decades, with ongoing changes in the prevalence of HEV. Method s : This study, in conjunction with the health examinations for students and workers, aims to estimate the seroprevalence and assess the risk factors of HEV infection in general population in Hebei province, China. Epidemiological information was collected using a specific questionnaire and blood samples were collected from each participant during the process of health examination. Anti‐HEV IgG and IgM in sera were tested using the Wantai ELISA assay kits. Logistic regression modelling was used to identify associated risk factors. Results: The average positive rate of anti‐HEV IgG in students (6–25 years) was 3.4%. One (0.2%) student was anti‐HEV IgM positive, while also testing positive for IgG. The HEV seroprevalence was not related to students' gender, school, or family residence. In occupational populations, the overall seropositivity rate was 13.3% for anti‐HEV IgG and 0.67% for IgM. HEV seropositivity increased significantly with age, ranging from 3.8% to 18.6% in age groups, and differed significantly among four occupation groups: farmers (17.6%), food supply workers (18.0%), other non‐farm workers (14.7%) and healthcare workers (5.9%) (p = 0.002). Multivariable logistic analysis confirmed the significant correlations of seroprevalence with age and occupation. Conclusions: The study found a low seroprevalence of HEV in children and young adults in Hebei Province, China. Advanced age correlates with higher seroprevalence in occupational populations, indicating an accumulation of HEV infection over time. Seroprevalence varied significantly among different occupation groups, suggesting the important role of occupational exposure for HEV infection. [ABSTRACT FROM AUTHOR]

Background and Aim:Hepatitis E virus (HEV) poses a global public health concern. HEV has a single serotype and 8 genotypes. There is inadequate knowledge about risk factors and zoonotic transmission pathways of hepatitis E virus in Mongolia, although the prevalence of HEV is, on average, 12% among the Mongolian population. This study aimed to estimate the prevalence and risk factors of HEV G8 infection in Bayankhongor province, Mongolia. Materials and Methods: Human serum samples (309) were collected in Bogd, Bayangovi, and Bayanlig districts of Bayankhongor province, Mongolia, with a control group consisting of non-camel herders. An in-house indirect enzyme-linked immunosorbent assay kit was used to detect anti-HEV IgG. The interviewer-administered questionnaire was used to gather the data. The assessment factors included age, sex, and occupation for the respondents. Univariate analyses were conducted using the Statistical Package for the Social Sciences version 26. The same population was tested for hepatitis B and C viruses (HBVs and HCVs) using rapid tests. Results: Of 309 samples, 41 (13.3%) tested positive for anti-HEV immunoglobulin G antibodies, 23 (7.4%) for HBV and 11 (3.6%) for HCV. HEV seropositivity was linked with water supply, khoormog consumption, and co-infection with HBV and HCV. Conclusion: HEV prevalence among Bayankhongor residents underscores potential transmission routes related to water supply and khoormog consumption, emphasizing the need for sequencing from human positive sera of HEV and preventive measures. We did not conduct the genotyping of positive human samples.

Abstract 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.

Background/Objectives: Hepatitis E virus (HEV) is an RNA virus recognized to be spread mainly by fecal-contaminated water. Its infection is known to be a serious threat to public health globally, mostly in developing countries, in which Africa is one of the regions sternly affected. An African-based vaccine is necessary to actively prevent HEV infection. Methods: This study developed an in silico epitope-based subunit vaccine, incorporating CTL, HTL, and BL epitopes with suitable linkers and adjuvants. Results: The in silico-designed vaccine construct proved immunogenic, non-allergenic, and non-toxic and displayed appropriate physicochemical properties with high solubility. The 3D structure was modeled and subjected to protein docking with Toll-like receptors 2, 3, 4, 6, 8, and 9, which showed a stable binding efficacy, and the dynamics simulation indicated steady interaction. Furthermore, the immune simulation predicted that the designed vaccine would instigate immune responses when administered to humans. Lastly, using a codon adaptation for the E. coli K12 bacterium produced optimum GC content and a high CAI value, which was followed by in silico integration into a pET28 b (+) cloning vector. Conclusions: Generally, these results propose that the design of an epitope-based subunit vaccine can function as an outstanding preventive vaccine candidate against HEV, although validation techniques via in vitro and in vivo approaches are required to justify this statement.

Abstract 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 log10IU/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.

Abstract The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division. The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG—28.9%, IgM—4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV. A temporal analysis (1987–2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden. These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies. Key points Research Question Investigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts. Findings Sporadic Transmission of IgG and IgM Prevalence: • Pooled anti-HEV IgG prevalence: 21.03% • Pooled anti-HEV IgM prevalence: 3.49% Seroprevalence among specific groups: High-risk group (farm workers and chronic patients): • anti-HEV IgG: 28.9% • anti-HEV IgM: 4.42% Low-risk group (general population, blood donors, pregnant women, hospital patients): • anti-HEV IgG: 17.86% • anti-HEV IgM: 3.15% Temporal Seroprevalence of HEV: Anti-HEV IgG prevalence increased over decades (1987–1999; 2000–2010; 2011–2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27% Importance Provides a comprehensive overview of HEV seroprevalence in Southeast Asia. Highlights variation in seroprevalence among different population groups. Reveals increasing trend in HEV seroprevalence over the years. Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics.

To determine the kinetics of hepatitis E virus (HEV) in asymptomatic persons and to evaluate viral load doubling time and half-life, we retrospectively tested samples retained from 32 HEV RNA-positive asymptomatic blood donors in Germany. Close-meshed monitoring of viral load and seroconversion in intervals of ≈4 days provided more information about the kinetics of asymptomatic HEV infections. We determined that a typical median infection began with PCR-detectable viremia at 36 days and a maximum viral load of 2.0 × 104 IU/mL. Viremia doubled in 2.4 days and had a half-life of 1.6 days. HEV IgM started to rise on about day 33 and peaked on day 36; IgG started to rise on about day 32 and peaked on day 53. Although HEV IgG titers remained stable, IgM titers became undetectable in 40% of donors. Knowledge of the dynamics of HEV viremia is useful for assessing the risk for transfusion-transmitted hepatitis E.

On March 31, 2022, severe acute hepatitis of unknown origin was first reported from the Royal Glasgow Children's Hospital in Scotland. According to the criteria by WHO‐ECDC, a probable case of unknown acute hepatitis in children is defined as a subject under 16 years of age, who tested negative for viral hepatitis and transaminases >500 U/L, starting from the 1st of October 2021. WHO invites Member States to participate in the global effort to collect anonymized clinical data on probable cases of severe acute hepatitis of unknown aetiology. As of May 26, 2021, 650 cases were already registered on the platform worldwide, of whom at least 38 cases have required liver transplants. Several hypotheses such as previous SARS‐CoV‐2 infection or coinfection or infection with another virus were examined and a strong association was found between adenovirus (41F) and acute hepatitis of unknown aetiology cases. This review article summarizes the global epidemiological evidences on acute hepatitis of unknown origin in children, analysing their incidence and characteristics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) genotype 3 is a prevalent zoonotic pathogen in European pig farms, posing a significant public health risk primarily through the foodborne route. The study aimed to identify effective biosecurity measures for controlling HEV transmission on pig farms, addressing a critical gap in current knowledge. Utilizing a cross-sectional design, fecal samples from gilts, dry sows, and fatteners were collected on 231 pig farms of all farm types across nine European countries. Real-time RT-PCR was employed to test these samples for HEV. Simultaneously, a comprehensive biosecurity questionnaire captured data on various potentialmeasures to control HEV. The dependent variable was HEV risk, categorized as lower or higher based on the percentage of positive pooled fecal samples on each farm (25% cut-off). The data were analyzed using generalized linear models (one for finisher samples and one for all samples) with a logit link function with country and farm type as a priori fixed factors. The results of the final multivariable models identified key biosecurity measures associated with lower HEV risk, which were the use of a hygienogram in the breeding (OR: 0.06, p=0.001) and/or fattening area after cleaning (OR: 0.21, p=0.019), the presence of a quarantine area (OR: 0.29, p = 0.025), testing and/or treating purchased feed against Salmonella (OR: 0.35, p = 0.021), the presence of other livestock species on the farm, and having five or fewer persons in charge of the pigs. Contrary to expectations, some biosecurity measures were associated with higher HEV risk, e.g., downtime of 3 days or longer after cleaning in the fattening area (OR: 3.49, p = 0.005) or mandatory handwashing for farm personnel when changing barn sections (OR: 3.4, p = 0.026). This novel study unveils critical insights into biosecurity measures effective in controlling HEV on European pig farms. The identification of both protective and risk-associated measures contributes to improving strategies for managing HEV and underscores the complexity of biosecurity in pig farming. [ABSTRACT FROM AUTHOR]

Detection methods have been developed to prevent transmission of zoonotic or xenozoonotic porcine viruses after transplantation of pig organs or cells to the recipient (xenotransplantation). Eleven xenotransplantation-relevant viruses, including porcine cytomegalovirus, porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses -1, -2, -3 (PLHV-1, 2, 3), porcine parvovirus (PPV), porcine circovirus 2, 3, 4 (PCV2, 3, 4), hepatitis E virus genotype 3 (HEV3), porcine endogenous retrovirus-C (PERV-C), and recombinant PERV-A/C have been selected. In the past, several pig breeds, minipigs, and genetically modified pigs generated for xenotransplantation had been analyzed using these methods. Here, spleen, liver, and blood samples from 10 German slaughterhouse pigs were screened using both PCR-based and immunological assays. Five viruses: PCMV/PRV, PLHV-1, PLHV-3, and PERV-C, were found in all animals, and PCV3 in one animal. Some animals were latently infected with PCMV/PRV, as only virus-specific antibodies were detected. Others were also PCR positive in the spleen and/or liver, indicative of an ongoing infection. These results provide important information on the viruses that infect German slaughterhouse pigs, and together with the results of previous studies, they reveal that the methods and test strategies efficiently work under field conditions. [ABSTRACT FROM AUTHOR]

A wide range of virus-like particles (VLPs) is extensively employed as carriers to display various antigens for vaccine development to fight against different infections. The plant-produced truncated variant of the hepatitis E virus (HEV) coat protein is capable of forming VLPs. In this study, we demonstrated that recombinant fusion proteins comprising truncated HEV coat protein with green fluorescent protein (GFP) or four tandem copies of the extracellular domain of matrix protein 2 (M2e) of influenza A virus inserted at the Tyr485 position could be efficiently expressed in Nicotiana benthamiana plants using self-replicating vector based on the potato virus X genome. The plant-produced fusion proteins in vivo formed VLPs displaying GFP and 4M2e. Therefore, HEV coat protein can be used as a VLP carrier platform for the presentation of relatively large antigens comprising dozens to hundreds of amino acids. Furthermore, plant-produced HEV particles could be useful research tools for the development of recombinant vaccines against influenza. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa (SSA), the (sub)genotypes A1, D3, and E of the hepatitis B virus (HBV) prevail. Individuals infected with subgenotype A1 have a 4.5-fold increased risk of HCC compared to those infected with other (sub)genotypes. The effect of (sub)genotypes on protein expression and host signalling has not been studied. Mass spectrometry was used to analyse the proteome of Huh7 cells transfected with replication-competent clones. Proteomic analysis revealed significantly differentially expressed proteins between SSA (sub)genotypes. Different (sub)genotypes have the propensity to dysregulate specific host signalling pathways. Subgenotype A1 resulted in dysregulation within the Ras pathway. Ras-associated protein, RhoC, was significantly upregulated in cells transfected with subgenotype A1 compared to those transfected with other (sub)genotypes, on both a proteomic (>1.5-fold) and mRNA level (p < 0.05). Two of the main cellular signalling pathways involving RHOC, MAPK and PI3K/Akt/mTOR, regulate cell growth, motility, and survival. Downstream signalling products of these pathways have been shown to increase MMP2 and MMP9 expression. An extracellular MMP2 and MMP9 ELISA revealed a non-significant increase in MMP2 and MMP9 in the cells transfected with A1 compared to the other (sub)genotypes (p < 0.05). The upregulated Ras-associated proteins have been implicated as oncoproteins in various cancers and could contribute to the increased hepatocarcinogenic potential of A1. [ABSTRACT FROM AUTHOR]

Simple Summary: As a zoonotic pathogen, the Hepatitis E virus (HEV) is extensively distributed worldwide. Animal infections are typically asymptomatic, while human infections can result in both acute and chronic viral hepatitis. The transmission pathway is typically a fecal–oral one. Pigs are the primary host of HEV genotype 4 (HEV-4), which primarily causes sporadic infections in China. The aim of this study was to evaluate HEV infection in certain farms in Guangdong, China. Twenty-five pig farms provided 1568 blood samples, of which 902 (902/1568, 57.53%) were positive for anti-HEV IgG. Such a high serum positive rate indicates that pigs in Guangdong are widely exposed to HEV, which is a considerable public health and safety concern. The Hepatitis E virus (HEV) causes acute and chronic Hepatitis E and is a global public health concern. HEV genotypes 3 (HEV-3) and 4 (HEV-4) are common to humans and animals, and domestic pigs and wild boars have been identified as the main reservoirs. However, limited information is available on the status of HEV infection in pigs, particularly in the Guangdong Province, China. This study aimed to investigate the seroprevalence of HEV in pig farms within the Guangdong Province. A total of 1568 serum samples were collected from 25 farms and tested for anti-HEV IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) results revealed that 57.53% (902/1568) of serum samples from 24 farms (24/25, 96%) were positive for anti-HEV IgG antibodies. Year, season, region, and age were all linked risk factors for HEV in Guangdong, with season and region showing more significant impacts. The results showing a high seroprevalence of HEV confirmed its circulation among domestic pigs in the Guangdong Province, China. The presence of this antibody indicates that HEV infection was or is present on farms, posing a risk of zoonotic transmission of HEV from pigs to exposed workers and from pork or organs to consumption. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nucleic acid‐amplification testing (NAT) is used for screening blood donations/donors for blood‐borne viruses. We reviewed global viral NAT characteristics and NAT‐yield confirmatory testing used by blood operators. Materials and Methods: NAT characteristics and NAT‐yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion‐Transmitted Infectious Diseases. Reported characteristics are presented herein. Results: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini‐pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT‐yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow‐up sample. Conclusion: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT‐yields, potentially benefitting blood operators seeking to implement NAT. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) poses a global threat, which currently remains understudied in terms of host interactions. Epidermal growth factor receptor (EGFR) plays multifaceted roles in viral pathogenesis, impacting host-cell entry, viral replication, and host-defense modulation. On the one hand, EGFR signaling emerged as a major driver in innate immunity; on the other hand, a crosstalk between HEV and EGFR requires deeper analysis. We therefore aimed to dissect the receptor’s involvement in the HEV life cycle. In persistently HEV-infected cells, the EGFR amount is decreased alongside with enhanced receptor internalization. As compared with the control ligand-induced EGFR, activation revealed an early receptor internalization and degradation in HEV-replicating cells, resulting in a notable EGFR signaling delay. Interestingly, inhibition or silencing of EGFR increased viral replication, extracellular and intracellular viral transcripts, and released infectious particles. The pro-viral impact of EGFR inhibition was attributed to (i) impaired expression of interferon-stimulated genes, (ii) activation of the autophagosomal system, (iii) virus-induced inhibition of lysosomal acidification, and (iv) a decrease of the cellular cholesterol level. IMPORTANCE This study identifies epidermal growth factor receptor (EGFR) as a novel host factor affecting hepatitis E virus (HEV): EGFR downregulation promotes viral replication, release, and evasion from the innate immune response. The discovery that EGFR inhibition favors viral spread is particularly concerning for HEV patients undergoing EGFR inhibitor treatment. [ABSTRACT FROM AUTHOR]