Several symptomatic cases of HEV infections were reported to the New Caledonia Island Public Health Service between August and December 2023. This prompted epidemiological and virological investigations to identify the source of infection.

HEV RNA was assessed in symptomatic patients, various food items, and pig farms on the Island. HEV strains were characterized by sequencing. A seroprevalence study was also conducted on asymptomatic blood donors before and after the outbreak. One hundred twenty-seven symptomatic cases were reported. Hospitalization was required for 29/127 patients (22.8%). Hospitalized patients presented more frequently with comorbidities, including liver and cardiovascular diseases (80.7% vs. 27%, p < 0.01), and 3 persons died (2.3%). Among the 100 HEV RNA-positive samples received at the French National Reference Centre for HEV, viral sequencing was possible for 76 samples. All strains were identified as HEV genotype 3, and 74/76 strains were grouped together (nucleotide identity: 98%-100%). Full-length sequencing indicated a new HEV-3 subtype within HEV-3 subclade abk. Only genotype 3f strains were detected on the Island's pig farms. No food items tested positive for HEV RNA. The seroprevalence of HEV IgG and IgM in blood donors was 9.2% (9/98) and 0%, respectively, in 2020, rising to 17.3% (17/98) and 2% (2/98) in 2024.

Although all previous large-scale epidemics in Asia and Africa were associated with HEV-1 or 2, the New Caledonia outbreak was linked to HEV-3. A high number of symptomatic cases were admitted to the hospital, with a case-fatality rate of 2.3%.

Introduction: Hepatitis E virus (HEV) infection is caused by viruses belonging to the Hepeviridae family. HEV infection can be self-limiting; however, extrahepatic manifestations may be present. The purpose of the current study was to establish the seroprevalence of HEV among Bulgarian liver transplant recipients (LTRs) and to identify associated risk factors. Materials & Methods: The present study was conducted between April 1, 2023, and October 30, 2023, at the Military Medical Academy, Sofia, Bulgaria. All serum samples were tested for anti-HEV IgG/IgM using HEV IgG/IgM enzyme-linked immunosorbent assay on Dia.Pro (Milan, Italy). Each participating LTR completed a detailed paper-based closed-ended questionnaire regarding the associated risk factors for HEV infection. Results: The study included 73 LTRs with a mean age of 47.0 ± 14.0 years. Anti-HEV IgG antibodies were detected in 25 LTRs (34.2%), including 20 males (37.7%) and 5 females (25%). All participants were HEV-IgM negative. HEV seropositivity rates were higher but not statistically significant in LTRs aged >60 years than in those aged <60 years (40% vs. 32.7%). A significant factor by logistic regression was "high level of education" (odds ratio [OR] = 2.917; p = 0.038). Conclusion: To the best of our knowledge, this is the first seroepidemiological HEV study among LTRs from Bulgaria that found a high seroprevalence (34.2%).

Hepatitis E virus (HEV) poses a significant risk to human health. In Europe, the majority of HEV infection are caused by the zoonotic genotype 3 (HEV-3), which can cause chronic hepatitis E in immunocompromised patients and those with pre-existing liver disease, and may eventually develop into fatal liver cirrhosis. In this study, we examined the effectiveness of a monoclonal antibody (MAb) treatment strategy using a well established HEV-3 pig model with intravenous infection. For this purpose, nine MAbs raised against the viral capsid protein were generated and the neutralizing activities were compared using in vitro assays. The antibody with the highest neutralizing activity, MAb 5F6A1, was selected for an in vivo study in pigs infected with HEV-3. Following the initial infection of pigs with HEV-3, MAb 5F6A1 was administered intravenously one and seven days post-infection. The results suggest MAb 5F6A1 significantly reduced viremia and virus shedding in pigs infected with HEV-3. This study provides significant insight into the dynamics of HEV infection in pigs and highlights the efficacy of MAb based therapy as an option for treating HEV in porcine hosts and, potentially, humans.

Chronic HEV infection is a significant cause of morbidity and mortality in immunocompromised patients, with rapid progression to advanced fibrosis. We present the case of a 71-year-old immunocompromised male with chronic liver disease due to hepatitis E, who experienced several episodes of HEV reactivation despite treatment with ribavirin. Thus, the treatment of the infection involves a challenge due to the lack of validated therapeutic options and the risk of viral reactivation after stopping treatment.

Herein, we reported the molecular characterization of HEV autochthonous strain from an immunocompetent patient. The HEV was classified as subtype 3c and displayed the V1479I ribavirin resistance mutation. The phylogenetic tree analysis showed two statistically supported clusters, including viral strains from symptomatic patients, without severe disease, and meat products.

Hepatitis E virus (HEV) infection is a frequent cause of acute viral hepatitis. Immunocompromised patients, especially those under anti-CD20 regimens, are prone to chronic or treatment-resistant courses of hepatitis E. We report a case of chronic HEV infection in a 36-year-old man with a history of thrombotic thrombocytopenic purpura treated with rituximab 6 months ago, who presented with new-onset painless jaundice and malaise. Laboratory tests and imaging revealed signs of inflammation and hepatic dysfunction. Due to initial suspicion of autoimmune hepatitis, corticosteroid therapy was started. However, liver biopsy and positive HEV RNA value redefined the diagnosis. Serology tests revealed initially acute infection, which later progressed to chronic hepatitis E infection. Treatment with ribavirin, along with supportive care, achieved significant clinical and laboratory improvement, resolving jaundice, restoring normal transaminase and suppressing HEV RNA values. Further review of the literature highlights the impact of immunosuppression caused by anti-CD20 therapies on HEV infection, as well as the challenges in both treatment and achieving sustained virus clearance in such patients. Moreover, this report underlines the importance of HEV screening in patients with hepatitis who have undergone anti-CD20 therapies, shedding light on a situation that is not well described in the literature and should not be overlooked, even in developed countries.

Hepatitis E virus (HEV) infection is a leading cause of acute hepatitis worldwide. Understanding of the mechanisms underlying productive HEV infection remains incomplete and would benefit from technological advances improving current model systems.

We exploited transposon-mediated random insertion and selection of viable clones to identify sites in the HEV open reading frame 2 (ORF2) protein, corresponding to the viral capsid, allowing for the insertion of reporter sequences in a functional context.

Short sequence insertions (5 amino acids) were tolerated at four distinct sites in the C-terminal region of the ORF2 protein, without significantly affecting viral capsid expression and subcellular localization as well as virus production. Full-length HEV genomes harboring larger sequence insertions such as an HA epitope tag, a highly sensitive miniaturized luciferase reporter (HiBiT) or a split GFP at these sites conserved their ability to produce infectious virus, with about a 1-log decrease in viral titers. Findings were confirmed in two different HEV genotype 3 clones. In addition, we demonstrate that HiBiT-tagged HEV, offering rapid and several-log amplitude detection, can be used for the evaluation of antiviral drugs and neutralizing antibodies.

We describe a convenient, quantitative and potentially scalable system for the monitoring of HEV infection and replication in tissue culture.

Hepatitis E virus infection is one of the most frequent causes of acute hepatitis and jaundice worldwide. As treatment options are limited and a vaccine is not universally available, the development of molecular tools to facilitate the identification of new therapeutic strategies is crucial. Based on a screening approach to identify viable insertion sites in the viral genome, we describe a versatile system for preparing recombinant viruses harboring split-reporter tags, i.e. luciferase and GFP. Proof-of-concept experiments revealed that convenient and quantitative monitoring of viral infection and replication is possible with this system, allowing for the evaluation of antiviral drugs and neutralizing antibodies.

Cancer patients with haematological malignancies are at risk for chronic hepatitis E virus infection following chimeric antigen receptor (CAR) T-cell therapy. Strong clinical suspicion is essential for the early diagnosis and prompt treatment of this difficult-to-treat type of viral hepatitis. Commentary on: Schwarz et al. Chronic hepatitis E in a patient after CAR-T cell treatment for diffuse large B-cell lymphoma and rapid progression towards decompensated liver cirrhosis. Br J Haematol 2025; 206:977-980.

Hepatitis E virus (HEV) is a major zoonotic pathogen causing hepatitis E, with strains identified in various animal species, including pigs, wild boar, rabbits, deer, camels, and rats. These variants are capable of crossing species barriers and infecting humans. HEV belongs to the family Hepeviridae, which has recently divided into two subfamilies: Orthohepevirinae and Parahepevirinae, and five genera: Paslahepevirus, Avihepevirus, Rocahepevirus, Chirohepevirus, and Piscihepevirus. Recent advances in high-throughput sequencing, particularly of bat viromes, have revealed numerous HEV-related viruses, raising concerns about their zoonotic potential. Bat-derived HEVs have been classified into the genus Chirohepevirus, which includes three distinct species. In this study, we analyzed 64 chirohepevirus sequences from 22 bat species across six bat families collected from nine countries. Twelve sequences represent complete or nearly complete viral genomes (>6410 nucleotides) containing the characteristic three HEV open reading frames (ORFs). These strains exhibited high sequence divergence (>25%) within their respective host genera or species. Phylogenetic analyses with maximum likelihood methods identified at least seven distinct subclades within Chirohepevirus, each potentially representing an independent species. Additionally, the close phylogenetic relationship between chirohepevirus strains and their bat hosts indicates a pattern of virus-host co-speciation. Our findings expand the known diversity within the family Hepeviridae and provide new insights into the evolution of bat-associated HEV. Continued surveillance of chirohepevirus will be essential for understanding its potential for zoonotic transmission and public health risks.

Hepatitis E virus (HEV) infection is endemic in China. However, there are scarce data of HEV infection among hospital attendees seeking medical treatment or examination for various reasons.

We aim to investigate the prevalence and incidence of HEV infection by time, age, sex, and across departments in a tertiary hospital.

Paired results of anti-HEV immunoglobulin G (IgG) and IgM of 31,181 unique subjects during 2021-2022 were analysed.

Overall seropositivity (95% confidence interval) of anti-HEV IgG and IgM was 41.25% (40.71%-41.80%) and 2.35% (2.19%-2.53%), respectively. Acute hepatitis E was more prevalent during winter-early spring and among adults aged 31-70. Anti-HEV IgG seroprevalence increased with age, levelling off at > 60 years of age. Not only the seropositivity, but also the levels of anti-HEV IgG were significantly lower in women than men of middle and old age. Young patients from the Department of Neurology had a significantly higher ratio of past HEV infection, while patients with manifestations of hepatitis, gastrointestinal symptoms or hematological diseases had higher seropositivity of anti-HEVIgM and should have high priority to HEV screening.

Heterogeneity of HEV seroprevalence was noted at different times of the year, between sexes, among age groups and across departments in general hospital. The concentration of HEV-infected patients in a few departments supports a more focused screening strategy in health-care settings.

Hepatitis E virus (HEV) infection is an important etiology of liver failure. This study aimed to explore the associations of blood fibrosis profiles with HEV-related liver failure (HEV-LF) onset and evaluate their prediction performance in hospitalized patients with acute hepatitis E.

Participants were obtained from two tertiary medical centers in Jiangsu, China, between January 2018 and November 2024. Cox proportional hazards regression, restricted cubic splines, and threshold effect analysis were used to examine associations between fibrosis markers and HEV-LF risk. The predictive value of these markers was evaluated for importance ranking, discrimination, calibration, and net benefit.

Among 504 included participants, 59 developed HEV-LF during hospitalization. After adjusting for covariates, elevated baseline laminin (HR = 1.432, 95% CI: 1.080-1.900), fibrosis-4 score (HR = 1.865, 95% CI: 1.375-2.530), and aspartate aminotransferase to platelet ratio index (APRI) (HR = 1.603, 95% CI: 1.315-1.954) were associated with a higher HEV-LF risk in a dose-dependent manner. Hyaluronic acid (≤ 740 ng/mL: HR = 1.797, 95% CI: 1.177-2.744) and type IV collagen (≤ 137 ng/mL: HR = 3.075, 95% CI: 1.709-5.533) showed nonlinear associations. APRI was ranked the highest in importance, and its combination with the other two top important markers provided good discrimination (7-day HEV-LF: AUROC = 84.98%, 95% CI: 78.55-91.41; 14-day HEV-LF: AUROC = 80.11%, 95% CI: 73.49-86.73), calibration, and clinical utility for predicting HEV-LF onset.

Several blood fibrosis markers are closely associated with HEV-LF risk and have promising predictive value. These findings may inform clinical risk stratification in patients with AHE.

Not applicable.

Thrombocytopenia is a common extrahepatic manifestation of hepatitis E virus (HEV) infection and is usually transient and self-limited. Thrombotic thrombocytopenic purpura (TTP) is a rare and lethal blood disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ involvement. The link between HEV infection and TTP is still unclear.

A 74-year-old female was referred to our hospital with complaints of fever, fatigue, nausea and jaundice for 10 days. Liver dysfunction, positive IgM and IgG of HEV, and HEV-RNA viremia prompted the diagnosis of acute hepatitis E, which was followed by a dramatic decline in the platelet count. The presence of schistocytes in the peripheral blood smear, along with decreased ADAMTS13 activity, strongly suggested a diagnosis of TTP. Combination therapy, including 2 courses of lymphoplasmapheresis (LPE), 4 courses of therapeutic plasma exchange, glucocorticoids and rituximab, was applied and contributed to the recovery of platelet. No recurrence of TTP was observed during the follow-up period. To date, this is first patient who developed the initial episode of TTP during the course of HEV viremia. In the meanwhile, LPE was used for the first time in the treatment of HEV-associated TTP.

This case highlights the necessity of ruling out TTP in hepatitis E patients with newly developed and severe thrombocytopenia and the values of LPE plus rituximab in treating such patients.

As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.

Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) primarily cause self-limiting acute hepatitis. However, studies have also reported chronic progression of HEV disease in immunocompromised patients. While considerable progress has been made in the treatment of HCV and HBV through the development of direct-acting antivirals (DAAs), challenges including drug resistance, incomplete viral suppression resulting in failure to achieve clearance and the lack of effective treatment options for HDV and HEV remain. Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to DAAs and aim to disrupt virus-host interactions by modulating host cell pathways that are hijacked during the viral replication cycle. The aim of this review is to provide a comprehensive overview about the major milestones in research and development of HTAs for chronic HBV/HDV and HCV infections. It also summarizes the current state of knowledge on promising host-targeting therapeutic options against HEV infection.

Acute hepatitis E infection (HEV), with its high incidence in Europe, should be considered as a differential diagnosis of acute viral hepatitis and can in some cases manifest with pronounced neurological symptoms.

We report on a 33-year-old female patient with severe arthralgia, myalgia, headache and psychomotor deterioration. Laboratory analyses showed elevated transaminases without signs of cholestasis. Acute hepatitis E virus infection was detected in serum. She reported fatigue and dysesthesias not responsive to analgesics. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. HEV RNA was detected in the CSF. The infection remained mild, but dysesthesias persisted. Eight weeks after the first admission, the symptoms worsened again. Complete and sustained remission was achieved following intravenous corticosteroid treatment.

In patients with acute neurological symptoms and liver enzyme elevation, HEV infection should be considered. Neurologic symptoms such as fatigue, arthralgia, myalgia and dysesthesia along with psychomotor retardation should prompt CSF analysis.

Hepatitis E virus (HEV) is a significant global health issue, impacting both low- and middle-income countries and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in low- and middle-income countries, whereas genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, whereas chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programmes remain limited.

This position paper was developed by the European Society of Clinical Microbiology and Infectious Diseases Viral Hepatitis Study Group through an extensive review of clinical data, safety profiles, efficacy, and immunogenicity of HEV vaccines. The study group focused particularly on high-risk and special populations, synthesizing global health insights and incorporating recommendations from the Strategic Advisory Group of Experts to formulate strategies for wider HEV vaccination use.

The position paper evaluates the efficacy and safety of HEV vaccines in both general and special populations. It identifies key barriers to the integration of HEV vaccines into routine immunization programmes, including infrastructure limitations, costs, and vaccine accessibility. The paper also proposes strategies to overcome these challenges and improve vaccine distribution. Furthermore, it addresses ways to enhance public awareness and international cooperation to promote HEV vaccination efforts globally.

European Society of Clinical Microbiology and Infectious Diseases Viral Hepatitis Study Group recommends HEV vaccination for high-risk groups, including women of childbearing age, patients with chronic liver diseases, and immunosuppressed individuals. Prioritizing investments in vaccine logistics, integrating diagnostics, and educational outreach can enhance uptake.

Hepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections.

In this retrospective study at two large hospitals, 512 patients with borderline and positive anti-HEV-IgM and 94 patients with positive HEV-PCR between January 1999 and May 2023 were included.

Detection by anti-HEV-IgM-ELISA led to a positive HEV-PCR in only 17.9 %. Amongst patients with positive HEV-PCR, 61 had underlying immunosuppression and 23 were patients after solid organ transplantation (SOT). All 13 patients with chronic HEV infections were immunosuppressed. Generally, immunosuppression led to higher HEV-RNA concentrations and a higher probability of receiving immediate treatment. However, all fulminant courses with liver failure happened in patients without immunosuppression. Immunocompetent patients showed symptoms more frequently and primarily had higher bilirubin levels indicating more severe liver damage. A risk factor for delayed or failed viral clearance after SOT was the administration of mTOR inhibitors.

Fulminant HEV infections happen primarily in immunocompetent patients. Nevertheless, immunosuppressed patients bear the risk of undetected, prolonged HEV infections, reflected by the rare occurrence of symptoms.

The question of whether to treat patients with chronic hepatitis B (CHB) during the immune tolerance (IT) period is a matter of ongoing debate, as it is difficult to discern different levels of liver disease severity. We created and assessed a novel diagnostic model for identifying significant liver tissue damage in individuals with CHB in IT phase.

From November 2018 to December 2022, a cross-sectional study of 311 patients with chronic hepatitis B virus infection (HBV DNA > 30 IU/mL) at Ningbo No. 2 Hospital, Ningbo, China, who underwent liver biopsy, including 44 patients in IT phase. Utilizing univariate regression analyses and logistics analysis, and model was developed and validated to predict the severity of hepatic inflammatory and fibrosis in CHB patients and in IT phase.

Chitinase 3-like Protein (CHI3L1), albumin (ALB), alanine transaminase (ALT) / aspartate aminotransferase (AST) were identified as independent predictors of liver lesion severity in CHB patients with IT. The three were combined to build the model (named as CAA index), which demonstrated good performance. The CAA index achieved an area under the receiver operating characteristic curve (AUC) of 0.916 (95 % CI, 0.820-1.000) and AUC of validation group was 0.875 (95 % CI, 0.683-1.000).

CHI3L1 serves as an independent measure of liver fibrosis and inflammation in CHB. This diagnostic model has some value in assessing the severity of the patient's liver lesion severity and may be a reliable non-invasive diagnostic model helping determine whether treatment is necessary among CHB patients in IT phase.

Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.

This is the first study to evaluate the adequacy and reliability of the ChatGPT and Gemini chatbots on viral hepatitis. A total of 176 questions were composed from three different categories. The first group includes "questions and answers (Q&As) for the public" determined by the Centers for Disease Control and Prevention (CDC). The second group includes strong recommendations of international guidelines. The third group includes frequently asked questions on social media platforms. The answers of the chatbots were evaluated by two different infectious diseases specialists on a scoring scale from 1 to 4. Cohen's kappa coefficient was calculated to assess inter-rater reliability. The reproducibility and correlation of answers generated by ChatGPT and Gemini were analyzed. ChatGPT and Gemini's mean scores (3.55 ± 0.83 vs. 3.57 ± 0.89, p = 0.260) and completely correct response rates (71.0% vs. 78.4%, p = 0.111) were similar. In addition, in subgroup analyses with the CDC questions Sect. (90.1% vs. 91.9%, p = 0.752), the guideline questions Sect. (49.4% vs. 61.4%, p = 0.140), and the social media platform questions Sect. (82.5% vs. 90%, p = 0.335), the completely correct answers rates were similar. There was a moderate positive correlation between ChatGPT and Gemini chatbots' answers (r = 0.633, p < 0.001). Reproducibility rates of answers to questions were 91.3% in ChatGPT and 92% in Gemini (p = 0.710). According to Cohen's kappa test, there was a substantial inter-rater agreement for both ChatGPT (κ = 0.720) and Gemini (κ = 0.704). ChatGPT and Gemini successfully answered CDC questions and social media platform questions, but the correct answer rates were insufficient for guideline questions.

Diagnostic uncertainty caused by the low positive predictive value of HEV-specific IgM antibody (Ab) testing in a low-prevalence setting. We investigated the utility of a two-step HEV IgM Ab testing approach for diagnosing HEV infection.

We retrospectively reviewed all adults who underwent HEV IgM Ab and/or HEV RNA testing from July 2013 through June 2023 at Mayo Clinic. Two-step HEV IgM testing involved initial testing using recomWell HEV IgM ELISA (Mikrogen, Neuried, Germany), with reflex to recomLine HEV IgM Strip (Mikrogen, Neuried, Germany) on all recomWell HEV IgM-reactive or IgM-equivocal specimens, as recomLine HEV IgM has higher specificity than recomWell HEV IgM but is more labor-intensive.

A total of 1640 patients had HEV IgM Ab or HEV RNA testing, including 1293 (79%) with only HEV IgM Ab testing, 213 (13%) with only HEV RNA testing, and 134 (8%) with both HEV IgM Ab and HEV RNA testing. Eighteen HEV infections were diagnosed with acute (N=16) and chronic (N=2) infections. Two-step IgM Ab testing did not identify 2 solid organ transplant recipients with chronic HEV infection. In acute HEV infection with HEV viremia, 3 out of 4 patients (2 solid organ transplant recipients and 1 patient with Guillain-Barre syndrome) were treated with ribavirin.

A two-step HEV IgM Ab test may accurately diagnose acute HEV infection in immunocompetent persons. However, this approach fails to identify chronic HEV infection in immunocompromised individuals who need HEV RNA testing to establish the diagnosis.

The occurrence of hepatitis E virus (HEV) in patients with Schistosomiasis mansoni (SM) is still poorly understood in Brazil. The objective of this study was to estimate the seroprevalence of anti-HEV IgG in patients with SM and its association with the periportal fibrosis (PPF), assessed by serum markers and ultrasound criteria. This cross-sectional study was carried out in an endemic area in Pernambuco, Brazil, with schistosomal patients who underwent coproscopic survey. Anti-HEV antibody IgG were evaluated by using ELISA (Euroimmun®, Lübeck, Germmany). In positive cases, HEV-RNA was tested by using real-time PCR. Among the 286 patients (60.8% women; 56% 18-44 years), 116 (40.6%) had advanced PPF (Niamey pattern D/E/F). Anti-HEV IgG was positive in 15 (5.24%), and all were HEV-RNA negative. Anti-HEV IgG was more frequent in patients with an advanced PPF (D/E/F) pattern (p = 0.034) and those with the largest spleen diameter (p = 0.039). In this study, the occurrence of anti-HEV IgG in patients with SM was higher than described in the same region and more frequent among patients with evidence of advanced liver fibrosis.

Hepatitis E virus (HEV) poses a serious threat to both public health and animal food safety, thereby highlighting the demands for rapid, sensitive, and easy-to-use detection. This study aimed to develop a One-Pot assay using CRISPR/Cas13a for detecting HEV RNA, suitable for point-of-care testing (POCT) in resource-limited settings. CRISPR/Cas13a combined with reverse transcription polymerase chain reaction (RT-PCR) and reverse transcription recombinase-aided amplification (RT-RAA) was applied to a One-Pot assay device. Additionally, a large cohort of HEV-infected patient (154) and animal (104) specimens was utilized for validation. The RT-PCR/RT-RAA + CRISPR/Cas13a assays for HEV RNA detection (genotypes: HEV-1, HEV-3, and HEV-4) were established, optimized, and validated, achieving a limit of detection (LoD) of 1 copy/μL and 100% specificity. In the application validation for HEV infection, the positive rates of the RT-PCR + CRISPR and RT-RAA + CRISPR assays were 98.6% and 89.6% for patients, and 96.6% and 88.8% for animals, respectively, which were superior to those of RT-qPCR. Furthermore, sample rapid lysis, reagent lyophilization, and the One-Pot device were integrated to construct a One-Pot assay with an LoD of 102 copies/μL. Despite slight decreases in sensitivity, the One-Pot assay significantly reduces the assay time to 35 min, making it easy to perform, minimizing contamination, and meeting the requirements for screening. We developed a One-Pot assay of HEV RNA using the CRISPR/Cas13a which effectively realizes a POCT test and maximizes the impetus for POCT implementation and shows potential as a valuable tool for detecting and monitoring HEV infection.

Vietnam's unprecedented demand for meat from livestock, including pigs and farmed wildlife, underscores the importance of understanding zoonotic reservoirs for hepatitis E virus (HEV). This study aimed to identify and characterize circulating zoonotic HEV in domestic pigs and wild boar to understand genotype frequencies, transmission dynamics, and associated human health burdens. Rectal swabs, feces, and liver samples from 415 pigs and 102 wild boars were collected across various farms and slaughterhouses in central and southern Vietnam and screened for HEV RNA using nested PCR. HEV RNA-positive samples underwent sanger sequencing and genotyping. Overall, 10% (n = 54/517) of samples were HEV RNA-positive, with wild boars exhibiting the highest HEV positivity rate at 25%, followed by domestic pigs at 7%. Southern Vietnam showed a higher HEV RNA positivity rate (20%) compared to central Vietnam (7%). Notably, rectal swabs demonstrated the highest positivity rate (15%), followed by feces (8%) and liver (4%). HEV-3a was the predominant genotype at 85%, followed by HEV-4b at 9% and HEV-3f at 6%. While HEV-3a was distributed across both central and southern Vietnam, HEV-3f was exclusively detected in central Vietnam, and HEV-4b was identified in wild boar in southern Vietnam. These findings underscore the substantial prevalence of HEV in wild boars, emphasizing their potential as crucial zoonotic reservoirs alongside domestic pigs. Further investigations involving occupationally exposed individuals in high-prevalence areas are warranted to evaluate the human health impact of zoonotic hepatitis E and inform preventive measures. Regular epidemiological studies are imperative for assessing the prevalence and transmission of zoonotic HEV infections among common reservoirs, thereby aiding in the prevention of spillover events within the community.

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.

MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited in Southern and Southeastern Brazil donated serum samples and were divided into four groups: (i) 20 negative subjects, (ii) 20 presenting hepatitis, (iii) 19 with COVID-19 and (iv) 11 with hepatitis and COVID-19. Three miRNAs (miR-122, miR-143 and miR-223) were evaluated using real-time PCR. Hematological and biochemical markers were also analyzed. MiR-143 and miR-223 were downregulated among the hepatitis/COVID-19 group (p < 0.05). A positive correlation was observed between miR-223 and lymphocytes. There was a negative correlation between alanine transaminase (ALT) and aspartate transaminase (AST) for miR-143 and miR-223 and gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and neutrophil/lymphocyte ratio (NLR) only for miR-223 (p < 0.05). For hepatic fibrosis (FIB-4), miR-122 and miR-143 had a greater association and miR-223 was more associated with a history of vaccination against COVID-19. MicroRNAs 143 and 223 could be useful as biomarkers for hepatitis coinfection with COVID-19.

Hepatitis E virus (HEV) is a major global health issue, with an estimated 20 million infections annually. Although polymerase chain reaction (PCR) is the diagnostic gold standard due to its precision, it is expensive and technically demanding. Antibody tests offer a more practical and cost-effective alternative, although their accuracy can vary due to factors, such as test manufacturer, antigen composition, HEV genotype, and host immune status.

A comprehensive search was conducted in PubMed, Cochrane, Scopus, and Web of Science databases. Studies included comparing the sensitivity and specificity of immunoglobulin M or immunoglobulin G antibody tests to PCR. Exclusion criteria were non-PCR comparisons, sample sizes under 10, IgA or antigen tests, non-human samples, or missing sensitivity and specificity data. Only English-language full-texts or abstracts were considered. Data analysis was performed using Meta-DTA v2.1.1 and Stata 16.0.

The meta-analysis evaluated 8054 blood samples from 21 studies. Immunoglobulin M antibody tests demonstrated an overall sensitivity of 83% (95% CI 76-88) and specificity of 98% (95% CI 97-99). Immunoglobulin G tests showed a sensitivity of 74% (95% CI 62-82) and specificity of 89% (95% CI 84-93). Among manufacturers, Wantai was the most accurate for immunoglobulin M detection, whereas MP led for immunoglobulin G. Notably, test sensitivity improved when the test protein genotype aligned with the HEV genotype.

This meta-analysis confirmed that antibody assays have a good sensitivity and high specificity to detect HEV infection in situations where PCR is not feasible, highlighting their potential as a practical diagnostic tool.

Chronic hepatitis virus infections remain a major public health problem, despite significant therapeutic advances over the past two decades. Considerable progress has been made in the treatment of chronic viral hepatitis, but continued efforts are needed to develop and bring to market new drugs to fill the gaps in the current therapeutic armamentarium. Thus, clinical trials to assess the safety and efficacy of these new therapeutic approaches, including the selection of reliable and objective treatment endpoints, are still needed. Virological biomarkers play an important role in the diagnosis, monitoring, and evaluation of antiviral treatment efficacy. They are often used as primary or secondary endpoints in the evaluation of new treatments for chronic viral hepatitis. However, these markers are not all equally informative. The aim of this review article is to provide a comprehensive overview of the available virological tests for chronic viral hepatitis due to hepatitis B, D, C and E viruses, the information they provide and lack, the specific challenges associated with each, and their use in clinical trials of new treatments.

Hepatitis E virus (HEV) is one of the major etiologies for acute liver failure. This multicenter retrospective cohort study aimed to investigate the associations of lipid profiles with the risk of HEV-related acute liver failure (HEV-ALF) among hospitalized patients with acute hepatitis E. A total of 1061 participants were obtained from three tertiary medical centers in Jiangsu, China, between February 2018 and May 2024. Univariate and multivariate Cox regression models were constructed to assess the associations between lipid profiles and the risk of HEV-ALF onset. The time-dependent area under the receiver-operating-characteristic curve (AUROC) and decision curve analysis were used to further evaluate the predictive value of blood lipids. After adjusting for potential confounders, total cholesterol (HR = 0.535, 95% CI: 0.437-0.656, p < 0.001), high-density lipoprotein-cholesterol (HR = 0.065, 95% CI: 0.027-0.154, p < 0.001), low-density lipoprotein-cholesterol (HR = 0.653, 95% CI: 0.512-0.833, p = 0.001), and apolipoprotein A (ApoA) (HR = 0.006, 95% CI: 0.002-0.020, p < 0.001) were significantly associated with a reduced risk of HEV-ALF. Moreover, blood ApoA exhibited excellent discrimination ability and net benefit for predicting 7-day (AUROC = 82.47%, 95% CI: 77.92-87.02) and 14-day (AUROC = 78.81%, 95% CI: 74.13-83.49) HEV-ALF onset. The findings may provide further evidence on the progression of HEV infection and future risk prediction.

HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potential of cellular protease during HEV infection.

Using our established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 suppressed HEV infections with an EC 50 of ~0.02 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells, was also observed in HepaRG and primary human hepatocytes. Furthermore, through time-of-addition and RNAscope experiments, we confirmed that HEV entry is blocked by inhibition of cathepsins. Cathepsin L (CTSL) knockout cells were less permissive to HEV, suggesting that CTSL is critical for HEV infection. Finally, we observed cleavage of the glycosylated ORF2 protein and virus particles by recombinant CTSL.

In summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor K11777, especially with its notable safety profile in primary cells, further underscores its potential as a therapeutic candidate.

Hepatitis E virus (HEV) reinfection is prevalent among the population, posing a significant burden on prevention and control efforts. In this study, we conducted a comprehensive analysis of data from China's Disease Prevention and Control Information System's infectious disease surveillance system to identify the epidemiological characteristics, spatiotemporal clustering, and high-risk populations of HEV reinfection. From 2005 to 2023, HEV reinfection in Zhejiang Province exhibited a fluctuating trend, peaking in 2020, with a 3-5-year lag compared to the pattern of HEV incidence. The Cox model indicated that individuals aged 40-50 and females are at higher risk of reinfection. Spatial autocorrelation was observed in reinfection cases from 2011 to 2016, with high-high clustering areas concentrated in downtown Hangzhou. Additionally, spatiotemporal scanning revealed that the clustering of reinfection cases has shifted from Hangzhou to coastal areas in recent years. Our findings suggest that targeted prevention and control measures for HEV rein fection should be implemented based on the characteristics of high-risk populations and spatiotemporal clustering patterns.

The purpose of this study was to investigate the HEV vaccination intention, its determinants, and overall influence mechanisms among childbearing-age women.

The current study was cross-sectional and conducted online from June 25, 2023 to September 25, 2023 in Nanjing, China. Logistic regression models were constructed to identify the intention-associated background factors. Technology Acceptance Model (TAM) and Theory of Planned Behavior (TPB) were integrated and expanded as TAM-TPB model to further investigate the determinants and overall influence mechanism of HEV vaccination intention among this population using structural equation modeling.

A total of 423 eligible participants were included in this study. High general HEV knowledge was independently associated with an increased intention to get HEV vaccination (OR = 1.97, 95 % CI: 1.11-3.58, P = 0.023). All the hypotheses proposed in the theoretical TAM-TPB model were supported, with perceived ease of use, perceived usefulness, attitude, subjective norm, and perceived behavioral control positively affecting the intention of HEV vaccination (all P values <0.05), while perceived risk (P = 0.003) exhibited an inverse association with HEV vaccination intention. The model achieved an acceptable fit, and the total explained variance of HEV vaccination intention was as high as 86.20 %. Moreover, no significant common method bias was observed.

This is the first theory-based study that explored the HEV vaccination intention, its determinants, and overall influence mechanism among childbearing-age women. The results of the current study are of great importance for improving the understanding of the HEV vaccination intention among females of childbearing age.

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

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

BackgroundHepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain.AimTo analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019.MethodsHospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997-2015 and 2016-19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease.ResultsHepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016-19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11).ConclusionsHepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.