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Hepatitis E virus (HEV) is a global health problem, causing an estimated 20 million infections annually. Thus, the management of HEV requires special consideration. In developed countries, hepatitis E is mainly recognized as a foodborne disease (mainly transmitted via undercooked meat consumption) that is generally caused by genotype 3 and 4 circulating in various animals, including pigs and wild boars. The current absence of officially recognized protocols for the analysis of HEV in foods and the lack of awareness of this disease among healthcare workers, together with the high percentage of asymptomatic cases, make HEV infection highly underestimated. Most HEV-3 infections in immunocompetent individuals are self-limited. Nevertheless, the possibility of serious forms of liver disease, especially in patients with co-morbidities, should be considered because it can lead to a fatal outcome. Here, we report a case of fatal hepatitis related to HEV-3 infection in a 67-year-old male patient with underlying chronic liver disease (CLD) and living in a region where a high prevalence and genetic heterogeneity of HEV-3 in wild boar has been recently demonstrated. Our case report describes the interdisciplinary approach used (from the diagnosis to the virus phylogenetic characterization) in order to improve epidemiologic HEV surveillance in central Italy. [ABSTRACT FROM AUTHOR]

Thalassemia is an inherited hematological disorder characterized by a decrease in the synthesis of or absence of one or more globin chains. Hepatitis E virus (HEV) is a major cause of acute viral hepatitis, constituting a major global health burden and emerging as a critical public health concern. HEV infection is mainly transmitted via the fecal–oral route; however, parenteral transmission through blood components has been reported in both developing and developed countries. Although HEV infection is typically self-limiting, immunocompromised individuals, patients with chronic liver disease, and thalassemic patients are at a heightened risk of contracting the infection and may develop chronic hepatitis and life-threatening complications that require treatment. The reported prevalence rates of HEV in thalassemia patients vary significantly by country. Age, gender, residential area, and the cumulative amount of blood transfusions received have been identified as associated risk factors for HEV infection. In order to enhance blood safety and ensure the protection of vulnerable patient populations, such as thalassemia patients, several countries have introduced universal or targeted HEV screening policies in blood donations. Other preventive measures include vigilant monitoring of thalassemic patients and screening for anti-HEV antibodies. The aim of this review is to explore the prevalence, risk factors, clinical impact and management of HEV infection in patients with thalassemia. [ABSTRACT FROM AUTHOR]

This review synthesizes current knowledge on the risks posed by viral foodborne infections associated with pork, emphasizing their global prevalence and the complexity of managing such pathogens. It covers a range of significant viruses, including hepatitis A and E, norovirus, rotavirus, sapovirus, enterovirus, astrovirus, and enteric adenovirus. The role of pigs as reservoirs for diverse pathogens with zoonotic potential further complicates safety challenges, extending risks to individuals involved in pork production and processing. Various factors influencing viral contamination throughout the meat production chain are explored, from farm-level practices to processing and handling procedures. Emphasis is placed on the critical importance of implementing effective control measures at each stage, including enhanced biosecurity, rigorous hygiene practices, and appropriate thermal processing techniques. Additionally, the need for improved surveillance and detection methods to effectively identify and monitor viral presence in meat products is highlighted. In conclusion, the necessity of adopting a One Health approach that integrates efforts in animal health, food safety, and public health to mitigate the risks of viral foodborne infections associated with meat consumption is underscored. This holistic strategy is essential for safeguarding consumer health and ensuring the safety of the global food supply. [ABSTRACT FROM AUTHOR]

In this review, recent advances in the combination of CRISPR–Cas systems with graphene-based electrolyte-gated transistors are discussed in detail. In the first part, the functioning of CRISPR–Cas systems is briefly explained, as well as the most common ways to convert their molecular activity into measurable signals. Other than optical means, conventional electrochemical transducers are also developed. However, it seems that the incorporation of CRISPR/Cas systems into transistor devices could be extremely powerful, as the former provides molecular amplification, while the latter provides electrical amplification; combined, the two could help to advance in terms of sensitivity and compete with conventional PCR assays. Today, organic transistors suffer from poor stability in biological media, whereas graphene materials perform better by being extremely sensitive to their chemical environment and being stable. The need for fast and inexpensive sensors to detect viral RNA arose on the occasion of the COVID-19 crisis, but many other RNA viruses are of interest, such as dengue, hepatitis C, hepatitis E, West Nile fever, Ebola, and polio, for which detection means are needed. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, primarily transmitted through contaminated water and food. In patients with chronic liver disease (CLD), HEV infection might worsen the prognosis. This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in CLD patients. A decision tree–Markov cohort model was used to assess the cost-effectiveness of universal-vaccination, vaccination-following-screening, and no-vaccination strategies in 100,000 CLD patients over their lifetimes, simulating cohorts aged ≥16 years, ≥40 years, and ≥60 years, based on the licensed vaccination ages and typical ages of CLD onset, from a societal perspective. Model parameters were retrieved and estimated from previous publications and government data. The outcomes included HEV-related cases, costs, and the incremental cost-effectiveness ratio (ICER). Compared to no-vaccination, universal-vaccination reduced HEV-related cases by 32.8% to 39.6%, while vaccination-following-screening reduced them by 38.1% to 49.3%. Furthermore, universal-vaccination showed ICERs of USD 6898.33, USD 6638.91, and USD 6582.69 per quality-adjusted life year (QALY) for cohorts aged ≥16, ≥40, and ≥60 years, respectively. Moreover, the vaccination-following-screening strategy significantly enhanced cost-effectiveness, with ICERs decreasing to USD 6201.55, USD 5199.46, and USD 4919.87 per QALY for the cohorts. Additionally, one-way sensitivity analysis identified the discount rate and utility for CLD patients as the key factors influencing ICER. Probabilistic sensitivity analysis indicated the vaccination-following-screening strategy was cost-effective with probabilities of 92.50%, 95.70%, and 95.90% for each cohort. Hepatitis E vaccination in CLD patients costs less than GDP per capita for each QALY gained in China. The vaccination-following-screening strategy may be the optimal option, especially in those over 60 years. [ABSTRACT FROM AUTHOR]

Viral hepatitis (A–E) presents a major global health challenge. In 2015, the World Health Organization (WHO) launched an initiative to eliminate viral hepatitis, with the aim of reducing new infections by 90% and deaths by 65% by 2030. Mexico is one of 38 focus countries identified by the WHO, collectively accounting for 80% of global infections and deaths. While hepatitis B and C are commonly diagnosed in Mexico, routine diagnosis for hepatitis D and E is lacking, with no specific epidemiological data available. In 2020, Mexico implemented the National Hepatitis C Elimination Program, focusing on preventing new infections, reducing complications like cirrhosis and hepatocellular carcinoma, ensuring access to treatment, and improving patient care. However, this program has not been extended to hepatitis B and E. Addressing the challenges of viral hepatitis control in Mexico requires increased resource allocation, expanded diagnosis, vaccination for hepatitis A and B, and treatment coverage for hepatitis B and C, along with multisectoral engagement. This work provides an overview of Mexico's response to the global initiative, highlighting its progress, challenges, and areas of opportunity. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) has become increasingly important in recent years in terms of risk for public health, as the main causative agent of acute viral hepatitis. It is a foodborne disease transmitted to humans through the consumption of contaminated water or contaminated food. Human-to-human transmission is sporadic and is linked to transfusions or transplants. The main reservoirs of the hepatitis E virus are domestic pigs and wild boars, although, compared to pigs, wild boars represent a lesser source of risk since their population is smaller and the consumption of derived products is more limited. These peculiarities often make the role of the wild boar reservoir in the spread of the disease underestimated. As a public health problem that involves several animal species and humans, the management of the disease requires an interdisciplinary approach, and the concept of "One Health" must be addressed. In this direction, the present review intends to analyze viral hepatitis E, with a particular focus on wild boar. For this purpose, literature data have been collected from different scientific search engines: PubMed, MEDLINE, and Google scholar, and several keywords such as "HEV epidemiology", "Extrahepatic manifestations of Hepatitis E", and "HEV infection control measures", among others, have been used. In the first part, the manuscript provides general information on the disease, such as epidemiology, transmission methods, clinical manifestations and implications on public health. In the second part, it addresses in more detail the role of wild boar as a reservoir and the implications related to the virus epidemiology. The document will be useful to all those who intend to analyze this infectious disease from a "One-Health" perspective. [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]

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]

The development of a hepatitis E vaccine is imperative given its prevalence and the heightened risk it poses to specific populations. Hepatitis E virus infection, though often self-limiting, poses a significant threat to pregnant individuals and immunocompromised populations. This review delves into the historical trajectory of hepatitis E vaccine development and explores its potential impact on at-risk populations. Historically, efforts to formulate an effective vaccine against hepatitis E have been underway to mitigate the severity of the disease, particularly in regions where the infection is commonplace. As a self-limiting disease, the necessity of a vaccine becomes more pronounced when considering vulnerable demographics. Pregnant individuals face heightened complications, with potential adverse outcomes for both mother and child. Similarly, immunocompromised individuals experience prolonged and severe manifestations of the infection, necessitating targeted preventive measures. This review aims to provide a comprehensive overview of the milestones in hepatitis E vaccine development. By examining the historical progression, we aim to underscore the critical need for a vaccine to safeguard not only the general population but also those at elevated risk. The elucidation of the vaccine's journey will contribute valuable insights into its potential benefits, aiding in the formulation of informed public health strategies to combat hepatitis E effectively. [ABSTRACT FROM AUTHOR]

Hepatitis E is a significant cause of acute hepatitis, contributing to high morbidity and mortality rates, and capable of causing large epidemics through fecal–oral transmission. Currently, no specific treatment for hepatitis E has been approved. Given the notably high mortality rate among HEV-infected pregnant women and individuals with underlying chronic liver disease, concerted efforts have been made to develop effective vaccines. The only licensed hepatitis E vaccine worldwide, the HEV 239 (Hecolin) vaccine, has been demonstrated to be safe and efficacious in Phase III clinical trials, in which the efficacy of three doses of HEV 239 remained at 86.6% (95% confidence interval (CI): 73.0–94.1) at the end of 10 years follow-up. In this review, the progress and challenges for hepatitis E vaccines are summarized. [ABSTRACT FROM AUTHOR]

Hepatitis E (Hepatitis E, HE) is an acute and chronic infectious hepatitis caused by hepatitis E virus (Hepatitis E Virus, HEV) infection, which is responsible for most acute hepatitis in the world and is a significant public health problem. The pathogen, HEV, has three Open Reading Frames (ORFs) ORF1, ORF2, and ORF3, each of which has a different function. Most of the current research is focused on ORF1 and ORF2, while the research on ORF3 is still relatively small. To provide more ideas for the study of HEV pathogenesis and the prevention and treatment of HE, this paper reviews the effects of ORF3 on the ERK pathway, growth factors, immune response, and virus release. [ABSTRACT FROM AUTHOR]

The global distribution of hepatitis E virus (HEV) is attributed to its capacity to spread through several routes of transmission; hemodialysis has gained increased amounts of attention in recent years. Although Mexico is considered a hyperendemic region for hepatitis E, no HEV surveillance is performed in the country. The frequency of HEV in hemodialysis (HD) patients has not been determined. Herein, we conducted a cross-sectional single-center analytical study including 67 serum samples from HD patients. Anti-HEV IgG and IgM antibodies and the viral genome were determined; partial regions within the HEV genome were sequenced for further phylogenetic analysis. Globally, 14.9% of the tested patients exhibited reactivity for IgG antibodies against HEV, and none showed reactivity to IgM. A total of 5.9% of the samples showed HEV genome amplification, and sequencing confirmed the identity of genotype 3; subsequent analysis of positive cases revealed two acute cases and chronic hepatitis E infection in one patient. Notably, the chronic patient was negative for anti-HEV IgG antibodies. Our findings highlight the importance of viral genome testing in HD patients and the need to establish guidelines for HEV detection in Mexico. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) poses significant health concerns worldwide, particularly among people living with HIV (PLWHIV), due to an increased risk of chronic infection and progression to cirrhosis in individuals with low CD4 cell counts. This study aimed to investigate the prevalence, chronicity potential, and risk factors of HEV infection among PLWHIV in Greece, where data are currently absent. A synchronic multicentric study encompassing five major Greek university hospitals was executed over 24 months, recruiting 696 PLWHIV participants. The prevalence of HEV IgG antibodies was 16.5%, with 8.6% showing evidence of acute HEV infection (HEV IgM). Active viral replication (HEV RNA) was present in 2.3% of the study population. Longitudinal analysis revealed that of the 25 initially anti-HEV IgM-positive individuals, only 3 seroconverted to IgG positivity, and among those with prior HEV RNA positivity (16), none showed evidence of active replication in subsequent tests. Comparative subgroup analysis highlighted the lack of significant differences in HIV-related parameters between HEV seropositive and seronegative individuals. Laboratory evaluations generally showed no significant disparities across most parameters; however, a higher seropositivity for Hepatitis A was observed in the HEV-positive subgroup. Our findings highlight a considerable prevalence of HEV among PLWHIV in Greece, with no observed cases of chronicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis E virus (HEV) infection with some Paslahepevirus balayani strains in humans is known to cause pregnancy mortality. New strains of Rocahepevirus ratti have been identified with zoonotic potential. It is currently unknown whether Rocahepevirus ratti strains can cause pregnancy mortality in humans in a similar manner as their Paslahepevirus relatives. Our presented research suggests that the emerging Rocahepevirus ratti strain LCK-3110 does not infect the human placental cell line (JEG-3), unlike Paslahepevirus balayani gt3 strains, suggesting it may not be as significant of a pregnancy risk as human HEV strains. Paslahepevirus balayani and Rocahepevirus ratti are genetically diverse species of hepatitis E virus [HEV]. Previously, only members of the Paslahepevirus genus were known to infect humans but recently some Rocahepevirus members have been found to be infectious to both immunocompromised and immunocompetent humans. Paslahepevirus balayani genotypes (gt) 1, 2, and 4 are known for their detrimental effects during pregnancy, causing pregnancy-related disorders. Recent findings have demonstrated the ability of Paslahepevirus balayani gt3 to replicate within placental cell lines, suggesting a direct effect on the placenta and fetus. To study whether zoonotic rat HEV strains possess a similar human-host placental tropism, we utilized JEG-3 cells to understand the replicative ability of an infectious clone of a recently reported strain of Rocahepevirus ratti, the LCK-3110 strain. Infectious cDNA clones of Pasla-, Avi-, and Rocahepevirus were transcribed and then, transduced into JEG-3 cells. Cells were harvested, and cell lysates were used for testing infectivity. Five days post-transfection or after inoculation onto naive HepG2/C3A cells, the cells were analyzed for infection. Replication in transduced JEG-3 cells and the infection potential in HepG2/C3A cells were assessed via an indirect immunofluorescence assay and a flow-cytometry assay. We found that the Rocahepevirus ratti LCK-3110 strain did not have efficient replication in JEG-3 cell cultures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the main cause of acute hepatitis in humans worldwide and is responsible for a large number of outbreaks especially in Africa. Human infections are mainly caused by genotypes 1 and 2 of the genus Paslahepevirus, which are exclusively associated with humans. In contrast, viruses of genotypes 3 and 4 are zoonotic and have their main reservoir in domestic and wild pigs, from which they can be transmitted to humans primarily through the consumption of meat products. Both genotypes 3 and 4 are widespread in Europe, Asia, and North America and lead to sporadic cases of hepatitis E. However, there is little information available on the prevalence of these genotypes and possible transmission routes from animal reservoirs to humans in African countries. We therefore analysed 1086 pig sera collected in 2016/2017 in four districts in Sierra Leone for antibodies against HEV using a newly designed in-house ELISA. In addition, the samples were also analysed for HEV RNA by quantitative real-time RT-PCR. The overall seroprevalence in Sierra Leone was low with only 44 positive sera and a prevalence of 4.0%. Two serum pools were RT-PCR-positive and recovered partial sequences clustered into the genotype 3 (HEV-3) of the order Paslahepevirus, species Paslahepevirus balayani. The results are the first evidence of HEV-3 infection in pigs from Sierra Leone and demonstrate a low circulation of the virus in these animals to date. Further studies should include an examination of humans, especially those with close contact with pigs and porcine products, as well as environmental sampling to evaluate public health effects within the framework of a One Health approach. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) represents an emerging risk in industrialized countries where the consumption of contaminated food plays a pivotal role. Quantitative real-time RT-PCR (RT-qPCR) is one of the most suitable methods for the detection and quantification of viruses in food. Nevertheless, quantification using RT-qPCR has limitations. Droplet digital PCR (ddPCR) provides the precise quantification of nucleic acids without the need for a standard curve and a reduction in the effect on virus quantification due to the presence of inhibitors. The objectives of the present work were (i) to develop a method for the absolute quantification of HEV in swine tissues based on ddPCR technology and provide internal process control for recovery assessment and (ii) to evaluate the performance of the method by analyzing a selection of naturally contaminated wild boar muscle samples previously tested using RT-qPCR. The method was optimized using a set of in vitro synthesized HEV RNA and quantified dsDNA. The limit of detection of the developed ddPCR assay was 0.34 genome copies/µL. The analysis of the wild boar samples confirmed the validity of the ddPCR assay. The duplex ddPCR method showed no reduction in efficiency compared to individual assays. The method developed in the present study could represent a sensitive assay for the detection and absolute quantification of HEV RNA in food samples with the advantage of presenting the co-amplification of internal process control. [ABSTRACT FROM AUTHOR]

Simple Summary: In surveillance studies conducted in industrialized EU nations, a rise has been noted in hepatitis E infections that are unrelated to travel. According to previous research studies, eating undercooked or uncooked meat and organs, as well as products from pigs or other wild animals (wild boars and deer), was predominantly linked to human hepatitis caused by the hepatitis E virus genotype 3. Furthermore, domestic pigs and wild boars represent nature's primary reservoirs of this virus, and the liver is the main organ for hosting this virus. The goal of this study conducted in Serbia was to detect HEV in pig liver samples from slaughterhouses, retail outlets, and environmental swabs over the course of a year. All positive HEV samples were measured and expressed as HEV gene copy numbers per gram of sample, and a representative number of samples were sequenced using the Sanger approach. A total of 45 HEV-positive samples were re-amplified using nested RT-PCR employing CODEHOP primers targeting ORF2 (493 nucleotides). The average prevalence of the HEV genotype 3 in all pig liver samples from the slaughterhouses was 29%, while HEV prevalence was 44% in liver samples from animals younger than 3 months. HEV RNA was found in thirteen out of sixty (22%) environmental swab samples that were taken from different surfaces along the slaughter line. Our findings confirmed seasonal patterns in HEV prevalence, with two picks (summer and winter periods) during the one-year examination. Among HEV-positive samples, the average viral particles for all positive liver samples was 4.41 ± 1.69 log10 genome copies per gram. Phylogenetic analysis revealed the majority of HEV strains (43/45) from Serbia were grouped in the HEV-3a subtype, while two strains were classified into the HEV-3c subtype, and one strain could not be classified into any of the HEV-3 subtypes. [ABSTRACT FROM AUTHOR]

The hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Seroprevalence in the liver transplantation setting varies according to the seroprevalence of the general population in different countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 10.2% of the recipients and in 9.7% of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation. [ABSTRACT FROM AUTHOR]

The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as combined vaccine candidates in rhesus monkeys. The HEV and HBV components consisted of 450 bps, neutralizing the epitope/s (NE) region, and 685 bps small (S) envelope gene-corresponding proteins, respectively. Three groups (n = 2 monkeys/group) were intramuscularly immunized with a total of three doses of NE Protein (Lipo-NE-P), NE DNA + Protein (Lipo-NE-DP), and each of NE and S DNA + Protein (Lipo-NES-DP), respectively, given one month apart. All immunized monkeys were challenged with 10,000 fifty percent monkey infectious dose of homologous HEV strain. Post-immunization anti-HEV antibody levels in monkeys were 59.4 and 148.4 IU/mL (Lipo-NE-P), 177.0 and 240.8 IU/mL (Lipo-NE-DP), and 240.7 and 164.9 IU/mL (Lipo-NES-DP). Anti-HBV antibody levels in Lipo-NES-DP immunized monkeys were 58,786 and 6213 mIU/mL. None of the challenged monkeys showed viremia and elevation in serum alanine amino transferase levels. Monkeys immunized with Lipo-NE-DP and Lipo-NES-DP exhibited a sterilizing immunity, indicating complete protection, whereas monkeys immunized with Lipo-NE-P showed limited viral replication. In conclusion, the liposome-complexed DNA-corresponding proteins of HEV and HBV induced protective humoral immune responses to both components in monkeys and are worth exploring further. [ABSTRACT FROM AUTHOR]

Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively (p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% (p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as Paslahepevirus balayani, pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. Rocahepevirus ratti, formerly known as Orthohepevirus C, is a single-stranded RNA virus, recently reassigned to Rocahepevirus genus in the Hepeviridae family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans. [ABSTRACT FROM AUTHOR]

Enteric viruses are the major cause of gastroenteritis and enteric hepatitis worldwide, but in some areas like Saudi Arabia, little is known about their presence in water sources. The available information from clinical samples is not enough to figure out their actual prevalence. The aim of this study was to gather information for the first time in Saudi Arabia on the presence of the Norovirus (NoV) genogroup GI and GII, hepatitis A virus (HAV), and hepatitis E virus (HEV) in water. For this purpose, thirteen monthly samples were collected from Lake Wadi Hanifa and surrounding wells from December 2014 to November 2015. Viruses were detected and quantified using real-time RT-qPCR. Despite HEV findings being anecdotic, our results highlight interesting behaviors of the other viruses. There was a higher prevalence of noroviruses in Wadi Hanifa samples than in well water samples (46.43% vs. 12.5% of NoV GI; 66.67% vs. 8.33% of NoV GII). On the contrary, similar levels of HAV positivity were observed (40.48% in surface water vs. 43.06% in well water). Also, a strong influence of flooding events on HAV and NoV GI occurrence was observed in both surface and well water samples, with NoV GII apparently not affected. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis E virus (HEV) is a public health problem worldwide, as it is an important food pathogen that humans can obtain from animals. The most common way to infect humans is by consuming contaminated, undercooked meat or raw meat from infected pigs. However, domestic cattle, small ruminants such as sheep and goats, and farm rabbits should not be underestimated as possible sources of HEV infection for humans. Many studies have detected HEV in milk from infected ruminants. Thus, the consumption of raw milk might lead to infection. Among livestock, chickens are susceptible to avian HEV, which can cause symptomatic disease but is not dangerous to humans. Avoiding eating undercooked meat from certain livestock species and following basic hygiene rules when in contact with animals that may be a source of HEV are effective preventive measures for hepatitis E in humans. Hepatitis E virus (HEV) is a public health problem worldwide and an important food pathogen known for its zoonotic potential. Increasing numbers of infection cases with human HEV are caused by the zoonotic transmission of genotypes 3 and 4, mainly by consuming contaminated, undercooked or raw porcine meat. Pigs are the main reservoir of HEV. However, it should be noted that other animal species, such as cattle, sheep, goats, and rabbits, may also be a source of infection for humans. Due to the detection of HEV RNA in the milk and tissues of cattle, the consumption of infected uncooked milk and meat or offal from these species also poses a potential risk of zoonotic HEV infections. Poultry infected by avian HEV may also develop symptomatic disease, although avian HEV is not considered a zoonotic pathogen. HEV infection has a worldwide distribution with different prevalence rates depending on the affected animal species, sampling region, or breeding system. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is now considered the most common cause of acute hepatitis worldwide. There are no published data about the prevalence of antibodies to HEV and RNA in donor sera in Estonia, and this precludes planning measures for preventing HEV proliferation through blood transfusion services. Here, were report data from an analysis of 1002 sera on the prevalence of anti-HEV IgG and IgM and the viral RNA. The antibodies were found in 48 donor sera (4.8%); of these, 40 (4%) harbored anti-HEV IgG, 15 (1.5%) contained anti-HEV IgM, and 7 donors had anti-HEV antibodies of both classes simultaneously. HEV RNA was not detected in any blood serum. Statistical associations of infection risk factors (gender, age, travel in the last six months, contact with pigs and/or wild boars in the last six months, consumption of thermally unprocessed/raw pork or boar meat, raw/unfiltered tap water or water from natural sources, unpasteurized farm dairy products, and unwashed berries and/or vegetables) were assessed. None of the listed factors were found to be associated with a higher or lower risk of anti-HEV antibody presence. At the same time, an increasing share of anti-HEV IgG carriers with age was found. The absence of HEV RNA in the analyzed donor plasma samples proves that HEV acute infection prevalence in Estonia does not exceed the average level of European countries. There is no urgent necessity to enter a requirement for a total screening of blood plasma for HEV RNA prevalence in Estonia. [ABSTRACT FROM AUTHOR]

A transversal study was conducted among 472 vulnerable individuals (recyclable waste pickers, immigrants and refugees, homeless individuals, as well as lesbian, gay, bisexual, and transexual individuals) in Goiânia City, the capital of the State of Goiás, Brazil, to investigate the prevalence of hepatitis E virus (HEV) infection. A total of 459 (97.2%) serum samples were tested for anti-HEV IgG and IgM antibodies using fully automated chemiluminescence immunoassays (Liaison® Murex Anti-HEV IgG and IgM assays, DiaSorin, Saluggia, Italy). Positive samples were tested for the presence of HEV RNA by a real-time polymerase chain reaction. A seroprevalence of 0.87% (95% confidence interval [CI]: 0.34–2.22) was found for anti-HEV IgG. Furthermore, anti-HEV IgM was detected in only one individual (0.22%; 95% CI: 0.04–1.22), who was also negative for HEV RNA. These findings revealed that HEV infection is infrequent in vulnerable individuals in Central Brazil, with low seroprevalence of past and recent HEV infections. [ABSTRACT FROM AUTHOR]

Hepatitis E virus genotype 3 (HEV-3) is a food-borne pathogen causative of hepatitis E infections in humans. In Europe, HEV-3 is mainly transmitted through the consumption of raw or undercooked pork. In order to determine the effectiveness of control measures that can be taken in the industry or by the consumer, it is pivotal to determine the infectivity of HEV present in pork products after thermal food-processing steps. First, we implemented a method for the detection of infectious HEV-3c and HEV-3e in a cell culture medium and in extracts from inoculated pork products. Next, we investigated the effect of the thermal inactivation of HEV by mimicking food-processing steps specific for dried sausage and liver homogenate matrices. After four weeks, HEV-inoculated dried sausage subjected to 21 °C or lower temperatures was still infectious. For the liver homogenate, the highest HEV-3c/e inactivation of the conditions tested was observed at 71 °C for five min or longer. Finally, our method was able to successfully detect and estimate viral loads of infectious HEV in naturally infected pig livers. Our data provide a basis for the future use of the quantitative microbial risk assessment of infectious HEV in pork products that are subjected to thermal food processing steps. [ABSTRACT FROM AUTHOR]

From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections often present as acute hepatitis with prodromal symptoms. These infections, transmitted via the oral–enteral route, constitute significant public health challenges, particularly in developing countries with subpar sanitary systems. The aim of the study was to describe the clinical manifestations, laboratory findings, and outcomes of hepatitis A and hepatitis E infections in Thailand. We conducted a retrospective chart review and analysis of 152 patients diagnosed with acute hepatitis A or hepatitis E from January 2007 to August 2018 at Siriraj Hospital. The hepatitis E cohort was older with a greater prevalence of comorbidities (hypertension, diabetes mellitus, chronic kidney disease, chronic hepatitis B, and post-kidney transplantation status) than the hepatitis A cohort. While the majority of hepatitis A patients presented with fever (98%) and jaundice (96%), these symptoms were less pronounced in hepatitis E patients. Furthermore, hepatitis A patients exhibited significantly higher aminotransferase and total bilirubin levels. However, clinical outcomes, such as hospitalization rates, progression to acute liver failure, and mortality, were comparable across both groups. In conclusion, although the clinical manifestations of hepatitis A and hepatitis E were similar, fever and jaundice were more prevalent and aminotransferase and bilirubin levels were higher in the HAV-infected group. [ABSTRACT FROM AUTHOR]

HEV is a single-stranded, positive RNA virus. The hepatitis E virus (HEV) is the causing agent of hepatitis, with a high prevalence rate in low-income countries due to poor sanitary conditions. It can exhibit acute, continuous, or extrahepatic consequences in immunocompromised individuals such as those undergoing organ transplantation and having HIV infection. HEV infection is either self limiting (silent), meaning the patient will possibly recover on his own, or symptomatic, causing acute liver injury or fulminant hepatitis and may eventually cause death. It can also cause chronic hepatitis that can progress to cirrhosis or recovery. Pregnancy-related HEV infection has an incidence rate of 30%. HEV escape from innate immunity, hormonal imbalances, defective monocyte–macrophage function, downregulation of the T-cell-mediated immune system, high cytokine production, nutritional factors, and socioeconomic conditions may play fundamental roles in the prevalence of HEV infection. It is necessary to take particular measures to reduce the incidence burden of HEV infection in high endemic locations as the incidence data, not the prevalence data, is more accurate at estimating disease dynamics. The purpose of this study is to throw light on several aspects of the hepatitis E virus and to discuss the incidence of HEV infection concerning other diseases. HEV molecular features, clinical features, epidemiology, extrahepatic manifestations, and multiple available diagnostics and treatment strategies for HEV are debated in the current review. [ABSTRACT FROM AUTHOR]

The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine. [ABSTRACT FROM AUTHOR]

Historically, viral hepatitis has been a considerable public health problem in Central Asian countries, which may have worsened after the dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of the seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n = 1075). Participants, children and adults, were recruited from an outpatient clinic. The data were collected during face-to-face interviews. A blood sample (6 mL) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D, and E). Post-stratification weighing was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval, 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV, and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg-positive participants, five (15%) were anti-HDV-positive. Our study confirms that Kyrgyzstan remains a highly endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development. [ABSTRACT FROM AUTHOR]

Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human–animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions. [ABSTRACT FROM AUTHOR]

The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations—kidney recipients (KR), patients with Guillain–Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)—were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations. [ABSTRACT FROM AUTHOR]

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E. [ABSTRACT FROM AUTHOR]

The identification of seven cases of hepatitis E virus infection in a French rural hamlet in April 2015 led to investigations confirming the clustering and identifying the source of the infection. Laboratories and general practitioners in the area actively searched for other cases based on RT-PCR and serological tests. The environment, including water sources, was also checked for HEV RNA. Phylogenetic analyses were performed to compare HEV sequences. No other cases were found. Six of the seven patients lived in the same hamlet, and the seventh used to visit his family who lived there. All HEV strains were very similar and belonged to the HEV3f subgenotype, confirming the clustering of these cases. All the patients drank water from the public network. A break in the water supply to the hamlet was identified at the time the infection probably occurred; HEV RNA was also detected in a private water source that was connected to the public water network. The water flowing from the taps was quite turbid during the break. The private water supply containing HEV RNA was the likely source of the contamination. Private water supplies not disconnected from the public network are still frequent in rural areas, where they may contribute to public water pollution. [ABSTRACT FROM AUTHOR]

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal–oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results. [ABSTRACT FROM AUTHOR]

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7—usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments—such as ribavirin—should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world. [ABSTRACT FROM AUTHOR]

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been implicated in promoting this persistence. The precursor of hepatitis e antigen (HBeAg), is translated from the precore/core region and is post-translationally modified to yield HBeAg, which is secreted in the serum. HBeAg is a non-particulate protein of HBV and can act as both a tolerogen and an immunogen. HBeAg can protect hepatocytes from apoptosis by interfering with host signalling pathways and acting as a decoy to the immune response. By evading the immune response and interfering with apoptosis, HBeAg has the potential to contribute to the hepatocarcinogenic potential of HBV. In particular, this review summarises the various signalling pathways through which HBeAg and its precursors can promote hepatocarcinogenesis via the various hallmarks of cancer. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis globally. Genotype 1 HEV (HEV-1) is responsible for multiple outbreaks in developing countries, causing high mortality rates in pregnant women. However, studies on HEV-1 have been hindered by its poor replication in cultured cells. The JE04-1601S strain recovered from a Japanese patient with fulminant hepatitis E who contracted HEV-1 while traveling to India was serially passaged 12 times in human cell lines. The cell-culture-generated viruses (passage 12; p12) grew efficiently in human cell lines, but the replication was not fully supported in porcine cells. A full-length cDNA clone was constructed using JE04-1601S_p12 as a template. It was able to produce an infectious virus, and viral protein expression was detectable in the transfected PLC/PRF/5 cells and culture supernatants. Consistently, HEV-1 growth was also not fully supported in the cell culture of cDNA-derived JE04-1601S_p12 progenies, potentially recapitulating the narrow tropism of HEV-1 observed in vivo. The availability of an efficient cell culture system for HEV-1 and its infectious cDNA clone will be useful for studying HEV species tropism and mechanisms underlying severe hepatitis in HEV-1-infected pregnant women as well as for discovering and developing safer treatment options for this condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis E virus (HEV) is a zoonotic pathogen, with an increasing number of cases worldwide. In Asia, including Mongolia, infections are associated with the zoonotic HEV-3 and HEV-4 genotypes, and pigs, deer, and wild boars are the main reservoirs. Recent studies have revealed that sheep are hosts of the virus in several countries. The aim of our study is to diagnose HEV RNA in feces and liver samples of sheep in Mongolia and clarify the origin of the virus and characterize its chain of infection. From our results, we found HEV genotype 4 in sheep and it was closely related to pig HEV genotype 4 in the same region. On Mongolian pig farms, pigs are fed with the raw internal organs of sheep for fattening the pigs as a free resource of protein. There is a concern that the spread of HEV could affect livestock feeding. Hepatitis E is a viral infectious disease in pigs, wild boars, cows, deer, rabbits, camels, and humans as hosts caused by Paslahepevirus. Recently, it has been detected in a wide variety of animals including domestic small ruminants. Mongolia is a land of nomadic people living with livestock such as sheep, goats, and cattle. Due to how Mongolian lifestyles have changed, pork has become popular and swine diseases have emerged. Among them, Hepatitis E disease has become a zoonotic infectious disease that needs to be addressed. The HEV problem in pigs is that infected pigs excrete the virus without showing clinical symptoms and it spreads into the environment. We attempted to detect HEV RNA in sheep which had been raised in Mongolia for a long time, and those animals living together with pigs in the same region currently. We also conducted a longitudinal analysis of HEV infection in pigs in the same area and found that they were infected with HEV of the same genotype and cluster. In this study, we examined 400 feces and 120 livers (pigs and sheep) by RT-PCR in Töv Province, Mongolia. HEV detection in fecal samples was 2% (4/200) in sheep and 15% (30/200) in pigs. The results of ORF2 sequence analysis of the HEV RT-PCR-positive pigs and sheep confirmed genotype 4 in both animals. The results suggest that HEV infection is widespread in both pigs and sheep and that urgent measures to prevent infection are needed. This case study points to the changing nature of infectious diseases associated with livestock farming. It will be necessary to reconsider livestock husbandry and public health issues based on these cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis E virus is one of the emerging pathogens causing lethal effects to pregnant and immunosuppressed individuals. Recent progress in HEV demonstrated the ability of the virus to cross the natural body barriers such as blood–brain and blood–testis barriers. Extrahepatic existence of HEV was related to clinical manifestations via different case reports, case–control studies, and prospective studies. Knowledge about HEV-related extrahepatic diseases is very important for clinicians, as this would give them a clearer picture of organs involved in hepatitis E virus pathogenesis and spread. This summarization of the extrahepatic replication sites will help in designing treatment regimens and selection of samples for screening of hepatitis E viruses in cases of sporadic outbreaks. Hepatitis E virus (HEV) is an emerging viral disease known to cause acute viral hepatitis globally. Various genotypes of HEV have been identified that produce genotype specific lesions depending on the HEV targeted population. Pregnant or immunosuppressed individuals develop significantly more severe hepatitis E in comparison to the general population. In the last 40 years, we discovered that the tropism of HEV is not restricted to the liver, and virus replication was demonstrated in multiple organs. Out of the 10 body systems described in humans, HEV produces lesions causing a broad range of extrahepatic clinical manifestations in each of them. Affected body systems include nervous and musculoskeletal, cardiovascular, digestive, endocrine, integumentary, renal, respiratory, immune, and reproductive systems producing systemic lesions. All extrahepatic signs are caused by either direct HEV replication in these tissues, or indirectly by various immune mediated mechanisms. Extrahepatic replication features of HEV allowed it to cross the placental barrier, blood–brain barrier (BBB), and blood–testis barrier (BTB) that do not typically grant entry to viruses in general. Thus, in this review, we summarized the extrahepatic replication sites of HEV, listed the body systems where HEV invaded, and described multiple animal models including immunocompetent and immunosuppressed that were used to study the extrahepatic replication sites of HEV. [ABSTRACT FROM AUTHOR]

Viruses are a leading cause of foodborne disease worldwide. Hepatitis viruses (hepatitis A (HAV) and hepatitis E (HEV)) and human norovirus are recognized as the main viruses of public health concern in food hygiene. ISO 15216 approved procedures are not validated for detection of HAV and human norovirus in foodstuffs, such as fishes, leading to an inability to ensure the safety of these products. This study aimed to provide a rapid and sensitive method for detecting these targets in fish products. An existing method that includes proteinase K treatment was selected for further validation using artificially contaminated fish products, according to the recent international standard ISO 16140-4. Recovery efficiencies in pure RNA extracts of viruses ranged from 0.2% to 66.2% for HAV, 4.0% to 100.0% for HEV, 2.2% to 100.0% for norovirus GI, and 0.2% to 12.5% for norovirus GII. LOD50 values were between 144 and 8.4 × 104 genome copies/g for HAV and HEV, and 104 and 2.0 × 103 copies/g for norovirus GI and norovirus GII, respectively. LOD95 values were between 3.2 × 103 and 3.6 × 105 genome copies/g for HAV and HEV, and between 8.8 × 103 and 4.4 × 104 genome copies/g for norovirus GI and norovirus GII, respectively. The method developed here was successfully validated in various fish products and can be applied for routine diagnostic needs. [ABSTRACT FROM AUTHOR]

One of the most intriguing issues in the hepatitis E virus (HEV) field is the significant increase in mortality rates of the mother and fetus when infection occurs in the second and third trimesters of gestation. A virus that is normally self-limiting and has a mortality rate of less than one percent in otherwise healthy individuals steeply rises by up to 30% in these pregnant populations. Answering this pivotal question has not been a simple task. HEV, in general, has been a difficult pathogen to understand in the laboratory setting. A historical lack of ability to efficiently propagate the virus in tissue culture models has led to many molecular aspects of the viral lifecycle being understudied. Although great strides have been made in recent years to adapt viruses to cell culture, this field remains behind other viruses that are much easier to replicate efficiently in vitro. Some of the greatest discoveries regarding HEV have come from using animal models for which naturally occurring strains of HEV have been identified, including pigs and chickens, but key limitations have made animal models imperfect for studying all aspects of human HEV infections. In addition to the difficulties working with HEV, pregnancy is a very complicated biological process with an elaborate interplay between many different host systems, including hormones, cardiovascular, kidneys, respiratory, gastrointestinal, epithelial, liver, metabolic, immune, and others. Significant differences between the timing and interplay of these systems are notable between species, and making direct comparisons between animals and humans can be difficult at times. No simple answer exists as to how HEV enhances mortality in pregnant populations. One of the best approaches to studying HEV in pregnancy is likely a combinatorial approach that uses the best combination of emerging in vitro and in vivo systems while accounting for the deficiencies that are present in each model. This review describes many of the current HEV animal model systems and the strengths and weaknesses of each as they apply to HEV pregnancy-associated mortality. We consider factors that are critical to analyzing HEV infection within the host and how, despite no perfect animal model for human pregnancy mortality existing, recent developments in HEV models, both in vitro and in vivo, are advancing our overall understanding of HEV in the pregnant host. [ABSTRACT FROM AUTHOR]

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016–2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6–7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients. [ABSTRACT FROM AUTHOR]