Search Results (379)

Hepatitis E virus (HEV) infection is generally self-limiting in immunocompetent individuals but may progress to chronic infection in immunocompromised patients, underscoring the need for effective antiviral therapies. Although ribavirin is currently used off-label for HEV treatment, its associated adverse effects highlight the need for safer alternatives. In this study, we screened an anti-viral compound library comprising 800 compounds using three HEV reporter systems designed to target distinct stages of the viral life cycle. Candidate compounds were further evaluated in PLC/PRF/5 cells using both acute and chronic infection models with wild-type genotype 3 HEV (HEV-3). Antiviral activity was assessed by measuring HEV RNA levels in culture supernatants. Elbasvir, a known inhibitor of hepatitis C virus (HCV) non-structural protein 5A (NS5A), was identified as the most potent candidate. Although multiple compounds showed inhibitory effects in reporter assays, only elbasvir achieved sustained suppression of HEV growth in long-term culture, reducing HEV RNA levels to below the limit of detection. In a chronic infection co-culture model, elbasvir maintained antiviral activity at non-cytotoxic concentrations. Time-of-addition analysis demonstrated that elbasvir inhibits an early step in the viral life cycle, specifically viral internalization. Furthermore, combination with ribavirin enhanced antiviral efficacy, resulting in sustained viral suppression without detectable cytotoxicity and exhibiting an additive interaction. Collectively, these findings identify elbasvir as a promising candidate for repurposing as an anti-HEV drug and support a combination strategy targeting distinct steps of the viral life cycle. Full article

Hepatitis E virus (HEV) is a major zoonotic pathogen, with pigs serving as the principal animal reservoir. While consumption of raw or undercooked pig liver is a well-recognized risk factor, systematic data on HEV contamination in retail pork meat remain limited. In this study, 1546 retail pork samples collected from eight geographic regions across Japan were analyzed for HEV RNA using a validated nested RT-PCR method. Analytical sensitivity was determined using the World Health Organization (WHO) International Standard for HEV RNA, yielding a 95% limit of detection (LOD95) of 134 IU/g (95% CI: 105–193). Overall, 15 samples (1.0%) tested positive for HEV RNA, with no significant regional variation (0.4–1.8%; p = 0.8375) or difference between domestically produced (1.0%, 12/1260) and imported pork (1.0%, 3/286; p = 0.7478). Viral loads in quantifiable samples (n = 11) ranged from 9.3 × 10² to 1.0 × 10⁵ IU/g. Genotyping based on partial ORF2 sequences revealed subtype 3b as predominant (n = 7), followed by 3a (n = 5), 3f (n = 2), and 4c (n = 1). Each of the 15 strains showed high nucleotide sequence identity (98.8–100%) to its closest reported Japanese strain(s). Phylogenetic analysis showed that all strains clustered with their closest reported HEV strains, with high bootstrap support, despite genetic diversity within subtypes. These findings demonstrate that retail pork meat in Japan is contaminated with HEV RNA and may represent a potential source of human exposure. However, whether HEV RNA-positive retail pork meat contains infectious virus capable of causing human infection remains to be determined. Full article

Hepatitis E virus (HEV) is a zoonotic cause of acute viral hepatitis that can become chronic in immunocompromised patients. Recently, host microRNAs (miRNAs) miR-122-5p, miR-125b-5p, miR-99a-5p, and miR-192-5p have been associated with acute HEV infection and with chronic HEV infection. Yet, the expression levels of miRNAs during the early phase of HEV infection remained unexplored. In this context, we aimed to identify changes in miRNA profiles occurring between the diagnosis of HEV infection and HEV cure in immunocompromised patients and in a pig model. We retrospectively included 9 immunocompromised patients with HEV infection (5 chronic and 4 resolutive) and 10 immunocompromised pigs (6 HEV-infected and 4 controls). RNAseq was retrospectively performed on pig samples. MiRNA expression was quantified by qPCR on pig and human samples.: Small RNA sequencing and targeted qPCR analyses revealed a pronounced, stage-dependent remodeling of miRNA expression during HEV infection. In patients, viral clearance was associated with early upregulation of miR-99a-5p, miR-122-5p, miR-125b-5p, and miR-194-5p, whereas progression to chronic infection was characterized by sustained downregulation of miR-23a-3p, miR-27a-3p, miR-106a-5p, miR-221-3p, and miR-223-3p. Likewise, a correlation was observed between the dysregulation of miR-181a-5p, miR-425-5p, and let-7b-5p with viral load (HEV RNA), while miR-27a-3p and miR-106a-5p were associated with ALT levels. In pigs, miR-122-5p was upregulated 10 weeks p.i., while 10 miRNAs (miR-16, miR-20a-5p, miR-23a-3p, miR-27a, miR-29a-3p, miR-140-5p, miR-181a, miR-191, miR-423-5p, and miR-99a-5p) were downregulated 11 weeks p.i. MiR-23a-3p, miR-27a, miR-99a-5p, miR-181a, and miR-425-5p were associated with HEV infection in both humans and pigs. Persistent HEV infection in immunocompromised patients and in a pig model showed partial overlap in miRNA responses. Our findings identified circulating miRNAs as stage-specific molecular markers of HEV infection in immunocompromised hosts. MiRNAs could contribute to early stratification of high-risk patients, improving outcomes for vulnerable patients facing this emerging viral disease. Full article

Hepatitis E is a liver inflammation caused by the hepatitis E virus (HEV). In pregnant women, the infection significantly increases the risk of acute liver failure, fetal loss, and maternal death. According to the World Health Organization, infection by HEV during the third trimester of pregnancy may increase the risk of maternal mortality in 20–25% of cases. In Tunisia, little is known about HEV infection and its outcome, especially in pregnant women. This study aims to evaluate the prevalence of HEV infection in a large cohort of pregnant women in Tunisia. A total of 891 women who attended the Centre of Maternity and Neonatology of Tunis during 2021–2023 were included. Serum samples were screened to detect HEV-antibodies and RNA using commercial ELISA tests and molecular assays, respectively. Statistical analyses were conducted using SPSS 21.0 software and the EPISTAT package version 7.2.6. Seroprevalence of HEV infection was 3.82%, based on the detection of anti-HEV IgG. The distribution of the seroprevalence according to age was statistically significant (p < 0.05), showing a higher seroprevalence among women over 30 years. Among the 51 women with composite outcomes, viral RNA was detected in one case by real-time RT-PCR. Our findings indicate a low HEV prevalence among pregnant women in Tunisia. Expanding the study to other cohorts and to environmental surveillance would improve understanding of HEV burden in Tunisia and support hepatitis elimination efforts. Full article

Hepatitis E virus (HEV) is an emerging zoonotic pathogen of increasing concern in developed regions and represents a major cause of acute viral hepatitis worldwide, primarily transmitted via the fecal–oral route. Although most infections are self-limiting, immunocompromised individuals, such as people living with human immunodeficiency virus (PLWH) and pregnant women, are at risk of severe outcomes, including chronic infection and fatal liver failure, respectively. This study was aimed at evaluating the prevalence and genetic diversity of HEV in PLWH and relevant ecological niches (swine and wastewater) in Venezuela. A total of 417 serum samples from PLWH, 85 wastewater samples, and 67 swine fecal samples were tested for serological or molecular HEV markers. The seroprevalence of anti-HEV antibodies among PLWH was 0.2% for IgM and 5.5% for IgG. HEV RNA was not detected in samples from PLWH or wastewater; however, a 1.5% prevalence of active infection was identified in swine. Phylogenetic analysis of a complete HEV genome revealed an unassignable subtype within genotype 3, tentatively designated as 3p. To the best of our knowledge, this study provides the first molecular characterization and report on HEV frequency in PLWH, wastewater, and swine in Venezuela. Full article

Hepatitis E virus (HEV) is the leading cause of hepatitis globally and poses particular risks for immunocompromised individuals. Mandatory screening of blood donations for HEV RNA and retrospective individual testing of previous donations (lookback investigations) following a reactive result have been implemented in several countries to protect these patients. This includes Germany, where a sensitivity limit of 2000 IU/mL applies to index donations. In total, 334 HEV RNA-positive blood donations were detected at our blood donation service between 2018 and 2024. Lookback testing was applied in 211 cases, revealing previous HEV RNA-positive donations in 23.1% of donors (n = 48, 76 donations). Although 16 of these retrospectively tested HEV RNA-positive donations have already been transfused, no transfusion-transmitted HEV infection has been reported. The HEV RNA viral load in the lookback donation was below 50 IU/mL in 72.4% of cases. Routine testing effectively prevents highly viremic blood products entering the supply, significantly reducing the infection risk. While the administration of virus particles with low-viremic products cannot be ruled out, the remaining risk appears to be minimal and has been deemed so far acceptable for the safety of blood products. The lookback strategy further supports the screening strategy by retrospectively identifying blood products from low-viremic donations and enabling appropriate risk management. Full article

Background: Hepatitis E virus (HEV) is an increasingly recognized cause of acute viral hepatitis in Thailand as the burden of hepatitis A, B, and C has declined. HEV is a positive-sense RNA virus in the family Hepeviridae with three major open reading frames encoding replication proteins (ORF1), the capsid protein (ORF2), and an accessory protein involved in viral egress (ORF3). Unlike highly endemic regions where genotypes 1 and 2 are linked to waterborne outbreaks, infections in Thailand are reported mainly as sporadic cases associated with zoonotic transmission, most commonly genotype 3. Objectives: This review summarizes the epidemiology, transmission routes, and public health implications of HEV infection in Thailand. Methods: Peer-reviewed studies on HEV seroprevalence, molecular epidemiology, and transmission in Thailand were identified through PubMed using combinations of the keywords “HEV” and “Thailand”. Two investigators independently screened titles, abstracts, and full texts. Eligible studies were synthesized qualitatively. Results: Earlier studies suggested low population exposure, but more recent evidence indicates substantial cumulative risk. A nationwide survey among blood donors reported anti-HEV IgG seroprevalence of about 30%, with geographic variation and increasing prevalence with age. Detection of HEV RNA in pigs, slaughterhouse environments, and retail pork products, together with links to raw or undercooked pork consumption, supports pigs as the principal reservoir and foodborne exposure as an important route. Transfusion-associated infection has also been documented. Conclusions: In Thailand, HEV infection is linked mainly to zoonotic and foodborne transmission involving genotype 3. Stronger surveillance, food safety measures, and risk-based blood safety policies are needed. Full article

Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients with acute hepatitis E from Craiova, Romania, with exploratory sex- and age-stratified analyses. Methods: We conducted a single-center retrospective observational study including 40 consecutive hospitalized patients with acute hepatitis E during 2024–2025. Admission and discharge laboratory values were compared at the within-patient level, and exploratory subgroup analyses by sex and age class were performed. Given the limited sample size, multivariable analyses were restricted to parsimonious age-adjusted models for selected endpoints. Results: The cohort comprised 22 females (55%) and 18 males (45%), with a mean age of 53.05 ± 21.44 years; two in-hospital deaths occurred. At admission, marked transaminase elevation and frequent hyperbilirubinemia were observed, with 70% of patients having total bilirubin ≥ 2 mg/dL and 40% ≥ 10 mg/dL. During hospitalization, ALT and AST declined markedly, whereas total and direct bilirubin improved more modestly, indicating slower resolution of jaundice/cholestatic abnormalities. Platelets increased, while prothrombin index changes were heterogeneous. Male patients had higher bilirubin values at admission and discharge and more frequent clinically relevant hyperbilirubinemia thresholds; however, these findings should be interpreted cautiously given the small sample size, the retrospective design, and the absence of standardized clinical confounders and mechanistic data. Exploratory age-stratified analyses did not identify robust differences after multiplicity control. Conclusions: In hospitalized hepatitis E, hepatocellular injury markers improved rapidly during hospitalization, whereas cholestatic abnormalities resolved more slowly and often remained clinically relevant at discharge. The observed sex-related cholestatic pattern should be considered exploratory and requires confirmation in larger studies with standardized clinical covariates and longer follow-up. These findings support closer monitoring of bilirubin trajectories at discharge, particularly in male patients, and highlight the need for integrating laboratory dynamics into short-term clinical assessment of hospitalized HEV cases. Full article

Shellfish are one of the important aquatic products in coastal areas. Due to their feeding mechanism, viruses can accumulate in their tissues during the feeding process. Most of the current research on HEV in shellfish is limited to the sampling of the surface layer to detect its prevalence, and traditional quantitative risk assessment methods face challenges in assessing the potential risks associated with consumption. Using the R language, we combined 2011–2024 literature detection data with experimental results to simulate infection risk for Chinese urban and rural residents under cooked and raw-consumption scenarios. Single-exposure infection probabilities were similar, but annual risks were comparable across groups. For urban residents, the 95% CrI of annual risk was 3.83 × 10⁻⁵ (2.5 × 10⁻⁶–3.56 × 10⁻⁴) (raw) and 1.2 × 10⁻⁸ (3.8 × 10⁻¹⁰–4.3 × 10⁻⁷) (cooked); for rural residents, the confidence interval was 2.69 × 10⁻⁵ (1.8 × 10⁻⁶–2.50 × 10⁻⁴) (raw) and 8.4 × 10⁻⁹ (2.5 × 10⁻¹⁰–3.0 × 10⁻⁷) (cooked). By assessing the prevalence of HEV in shellfish and the probability of infection after consumption, the safety awareness of the Chinese population regarding shellfish consumption can be strengthened. Also, suggestions can be derived from HEV prevalence data in various countries, to improve the breeding environment and reduce relevant prevalence and risks. Full article

Hepatitis E virus (HEV) is recognized as one of the leading causes of acute viral hepatitis (AVH) in developing countries, where it is primarily transmitted through the consumption of contaminated food and water. Although often self-limiting, HEV infection poses a significant public health concern, particularly among pregnant women, due to its potential complications. The present study aimed to determine the seroprevalence of HEV infection in asymptomatic antenatal women attending a tertiary care center in South Punjab, Pakistan. A total of 100 asymptomatic pregnant women were screened for anti-HEV antibodies (IgM and IgG) using an ELISA kit (DIA PRO, Italy). The overall seropositivity rate was found to be 12%, indicating prior exposure to HEV infection in this cohort. Specifically, IgG antibodies were detected in 6% of women and IgM antibodies in 5%, while two women showed evidence of both IgG and IgM positivity, suggestive of recent or ongoing infection. Notably, the majority of participants reported reliance on untreated water sources irrespective of educational background, highlighting environmental risk factors. Although HEV is generally self-limiting, these findings underscore the importance of routine serological screening in antenatal populations to prevent adverse pregnancy outcomes. In addition, increased community awareness regarding transmission routes and preventive measures is essential. Given the scarcity of regional data, this study emphasizes the need for larger-scale epidemiological investigations to better understand the burden of HEV in South Punjab, Pakistan. Full article

Cedar virus (CedV), related to the highly pathogenic bat-borne henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), is non-pathogenic in small animal models, likely due to the inability to produce interferon-antagonist proteins. We evaluated the pathogenesis of recombinant CedV (rCedV) in the African green monkey (AGM) model and determined if prior infection conferred cross-protective immunity against a lethal challenge with NiV Bangladesh (NiV-B) or HeV. AGMs infected with rCedV remained asymptomatic, with no clinical signs of disease or detectable viremia. The rCedV infected animals developed homologous neutralizing antibody responses that failed to cross-neutralize NiV-B or HeV. At 42 days post-rCedV infection, AGMs were challenged with a lethal dose of NiV-B or HeV, and prior infection with rCedV failed to protect against NiV-B challenge, with all animals succumbing to NiV-B. Similarly, rCedV infection did not confer consistent protection against HeV, with 2/4 animals succumbing to lethal HeV. These findings confirm that CedV is non-pathogenic in the AGM model of NiV and HeV infection, justifying its classification as a BSL-2 agent. The findings also demonstrate that rCedV does not elicit a cross-protective immune response to prevent lethal disease from either NiV-B or HeV highlighting significant immunological differences between CedV and the pathogenic henipaviruses. Full article

Hepatitis E virus (HEV) is a global public health concern, causing over 20 million infections annually. It is primarily transmitted via the fecal–oral route, with wild boars and domestic swine as major reservoirs involved in zoonotic transmission. Bahía de Samborombón is an important natural reserve in Argentina characterized by a high population of wild boars, located in a livestock-intensive region near major urban centers. As part of a wild boar control program, 11 sampling campaigns were carried out between 2022 and 2023. Fecal, blood, and liver samples were systematically collected from 80 captured animals for the detection and characterization of HEV through antibody and RNA testing. Serological analysis revealed a positivity rate of 42.4%, whereas RT-qPCR detected HEV RNA in 9.1% of fecal samples and 12.5% of liver samples. From the positive samples, seven viral sequences were recovered using RT-nested PCR, including six from ORF1 and one from ORF2. Phylogenetic analysis clustered these sequences within zoonotic HEV genotype 3, showing a close relationship with human sequences from Buenos Aires and neighboring provinces. This study confirms the presence of HEV in wild boars from Argentina, highlighting the circulation of genotype 3, clade abchijklmno and the associated zoonotic risk. Full article

The hepatitis E virus (HEV) is an emerging multi-host pathogen, with suids being the main reservoir. Humans are primarily infected through the consumption of contaminated water or food. In Argentina, HEV circulation has been confirmed in humans, domestic pigs, wild boar (Sus scrofa), and surface water. In El Palmar National Park, invasive wild boar and axis deer (Axis axis) are controlled, and their meat is released for public consumption, with trimmings and offal frequently fed to dogs. Between 2017 and 2019, we conducted a multi-species serological survey in this protected area to assess HEV exposure in invasive mammals and in dog and human consumers of game meat. We also evaluated associations between seropositivity and environmental variables, as well as behavioral risk factors among game-meat consumers. Total anti-HEV antibodies were detected in 29/75 (38.67%) wild boar, 1/134 (0.75%) deer, 1/18 (5.6%) dogs, and 6/59 (10.17%) humans. A spatial cluster of seropositive wild boar was identified in a low-lying, flood-prone area near the confluence of the El Palmar stream and the Uruguay river, suggesting increased risk of environmental transmission. This is the first report of HEV exposure in wild boar from this park and in axis deer and dogs in Argentina. Participation in culling and game meat handling and consumption may contribute to HEV exposure pathways among humans. These findings improve understanding of HEV epidemiology at the wildlife–domestic animal–human interface and highlight the influence of environmental factors and human behavior on zoonotic virus circulation. Full article

Hepatitis E virus (HEV) is an important cause of acute and chronic hepatitis worldwide, transmitted primarily through waterborne exposure and zoonotic foodborne pathways. In recent years, shellfish have attracted growing attention as a potential vehicle for HEV transmission. This interest is driven by epidemiological observations linking shellfish consumption to human HEV infection and by repeated detection of HEV RNA in bivalve mollusks across multiple geographic regions. This review critically evaluates the current evidence by integrating epidemiological data, environmental and food surveillance studies, and mechanistic insights into viral accumulation in shellfish. Signals from outbreak investigations, observational studies, seroepidemiological surveys, and case reports suggest that shellfish may contribute to HEV exposure. However, these findings are largely associative, methodologically heterogeneous, and limited by the absence of explicit documentation of raw or undercooked shellfish consumption in many cases. To date, no study has recovered infectious HEV from shellfish, nor has any established molecular epidemiological linkage between shellfish-derived HEV and human infections. Mechanistic knowledge from norovirus and hepatitis A virus demonstrates that bivalves can bioaccumulate enteric viruses through filter feeding, yet HEV-specific processes governing viral binding, persistence, and infectivity within shellfish remain poorly defined. Surveillance data reveal marked geographic variation in HEV RNA detection among shellfish species and production areas. Overall, existing evidence supports shellfish as a biologically plausible but unconfirmed source of HEV exposure. Addressing key knowledge gaps—particularly through direct infectivity assessments and high-resolution molecular linkage studies—will be essential to determine the public health significance of shellfish within the broader ecology of HEV transmission. Full article

Hepatitis E virus (HEV) is a significant public health concern and a leading cause of acute viral hepatitis worldwide. In recent years, HEV has been increasingly recognized as a wildlife-associated zoonotic pathogen, with numerous free-ranging species contributing to its maintenance and transmission. While domestic pigs remain the primary reservoir for human infection globally, growing evidence indicates that wild animals, particularly wild boars, cervids, lagomorphs, rodents, and carnivores, play a critical role in the ecology of HEV. Wild boars are the principal wildlife reservoir, with HEV seroprevalence in Europe ranging from less than 5% to more than 50%, including some of the highest levels reported in the Balkans. In addition to the frequent detection of HEV RNA in wild boar liver and muscle, viral RNA has also been identified in several other game species, most consistently in red deer, roe deer, and, in some regions, hares and wild rabbits, highlighting food safety risks associated with the consumption of raw or undercooked game meat. In regions such as the Balkans, where hunting activities and handling of wild game are widespread, these practices may further increase occupational and dietary exposure to HEV. Rodents may further complicate the epidemiological landscape through environmental contamination of water, soil, and farm surroundings, thereby facilitating indirect transmission pathways. As wildlife populations expand and human–animal interfaces intensify, understanding HEV dynamics in free-ranging species is essential for assessing zoonotic risks and implementing a strengthened One Health approach. This narrative review synthesizes and critically examines current evidence on HEV prevalence, molecular characteristics, and transmission pathways in wildlife, with particular emphasis on Europe and focused consideration of the Balkans as an epidemiologically heterogeneous and underrepresented subregion; examines associated public health implications; and highlights the importance of integrating wildlife into food safety and One Health surveillance frameworks. Existing knowledge gaps and limitations in wildlife surveillance are also discussed. Full article