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.

Early identification of patients with acute hepatitis E (AHE) who are at high risk of progressing to hepatitis E virus-related acute liver failure (HEV-ALF) is crucial for enabling timely monitoring and intervention. This multicentre retrospective cohort study aimed to develop and validate an interpretable machine learning (ML) model for predicting the risk of HEV-ALF in hospitalised patients with AHE in tertiary care settings.

The study cohort included patients admitted to seven tertiary medical centers in Jiangsu, China, between 01 January 2018 and 31 December 2024. Multiple ML algorithms were applied for feature selection and model training. The predictive performance of the models was evaluated in terms of discrimination, calibration and clinical net benefit. The interpretability of the final model was enhanced using the SHapley Additive exPlanations.

A total of 1912 participants were included in the study. Ten ML models were developed based on seven consensus-selected baseline features, with the survival gradient boosting machine (GBM) demonstrating superior performance compared to the traditional Cox proportional hazards regression model and other relevant models or scores. The GBM model achieved a Harrell's concordance index of 0.853 (95% CI: 0.791-0.914) in the external validation set. To facilitate clinical application, the GBM model was interpreted globally and locally and deployed as a web-based tool using the Streamlit-Python framework.

The GBM model demonstrated excellent performance in predicting HEV-ALF risk in hospitalised patients with AHE, offering a promising tool for clinical decision-making.

Hepatitis E virus (HEV) is a cause of enterically transmitted hepatitis around the world. Because of the high frequency of asymptomatic infections, the magnitude of HEV infection is underestimated. Wastewater monitoring could be useful to improve our knowledge on HEV epidemiology. In this study, we analyzed the capacity of wastewater surveillance to give an insight into the circulation and the diversity of HEV in two French cities. HEV RNA was detected and quantified by digital PCR in 115 untreated composite wastewater samples collected weekly at the inlet of wastewater treatment plants (WWTPs), 58 at Toulouse WWTP and 57 at Dunkerque WWTP. Plasma HEV RNA in blood donors was detected by a commercial assay (Roche Cobas) over the same period in the same area. HEV diversity was analyzed using long-read single-molecule real-time sequencing (Pacific Biosciences). HEV RNA was detected in 88% and 95% wastewater samples collected at Toulouse (Occitanie region, Southern France) and Dunkerque (Hauts-de-France region, Northern France) WWTPs, respectively. HEV RNA concentration ranged between 4.1 and 5.7 log copies/L and was almost similar between the two sites. A long orf2 fragment of HEV genome (1030 nucleotides) was obtained and sequenced in 45% and 70% of positive HEV RNA wastewater samples collected at Toulouse site and Dunkerque site, respectively. Out of 31 strains identified in Toulouse wastewater, 24 were HEV-3c (77%), 6 were HEV-3f (19%), and 1 was HEV-3h (3%). Out of 55 strains identified in Dunkerque, 30 were HEV-3c (55%) and 25 were HEV-3f (45%). All HEV RNA-positive samples from blood donors that could be genotyped during the study period contained HEV-3. Subtype distribution in 51 blood donors living in Toulouse did not differ from that in Toulouse wastewater. The HEV-3 subtype distribution in 51 Hauts-de-France region blood donors and in Dunkerque wastewater were different, but the predominant subtype was the same (HEV-3c). Lastly, we explored the link between the measurement of viral loads in wastewater and the extent of infection in the served population. Although a good correlation between the peaks of positive HEV RNA estimated in wastewater samples and that observed in blood donors was observed with a lag of + 3 weeks for Toulouse, the correlation was weaker for Dunkerque. Wastewater surveillance system applied locally could be very useful for assessing the HEV infection status of a population.

Hepatitis E virus (HEV) typically induces self-limiting infection but can establish persistent infection, particularly in patients with compromised immune systems. However, the literature on HEV infection in patients undergoing chemotherapy is limited.

A 46-year-old Chinese male patient with rectal cancer underwent ten cycles of chemotherapy and targeted therapy. Routine blood tests revealed grade 4 bone marrow suppression necessitating emergency admission. On the second day following admission, the patient presented with high fever that was determined to be chemotherapy-induced febrile neutropenia (FN). However, despite the recovery of white blood cell counts, the fever persisted, and the levels of aminotransferases and bilirubin continued to rise. Two weeks after admission, next generation sequencing of blood samples revealed evidence of HEV. The patient underwent symptomatic and supportive treatment and was discharged after a 30-day hospitalization. One month after discharge, the transaminase and bilirubin levels were within the normal range.

The fatality rate of FN is alarmingly high. To prevent progression to sepsis syndrome and potential mortality, it is imperative to initiate empirical treatment with broad-spectrum antibiotics. As the differential diagnosis of elevated liver enzymes in immunocompromised patients encompasses a wide range of possibilities, the exclusion of HEV infection is crucial when diagnosing drug-induced liver injury (DILI).

This case highlights the importance of healthcare providers being vigilant in identifying HEV infection in patients with solid tumors who experience FN and DILI. Early implementation of comprehensive supportive treatment is crucial for reducing the duration of disease and enhancing patient prognosis.

French Guiana (FG), a French overseas territory located in the Amazon region, is characterized by a high level of precariousness, which may be conducive to hepatitis E virus (HEV) transmission, but no recent relevant data exist.

We conducted a retrospective study to determine the incidence of acute HEV infection diagnosed at Cayenne Hospital, FG between 2015 and 2022.

Among 934 tested individuals, 12 had positive anti-HEV IgM (positivity rate of 1.28 % CI95 [0.66-2.23]). RT-PCR was rarely performed and no results was positive. Median age was 41 years and half of the subjects were female. No fulminant hepatitis occurred. Neurological manifestations were reported in two patients. Acute forms of HEV infection were rarely diagnosed during the study period.

Earlier and more extensive use of RT-PCR could help to better understand the epidemiology of acute HEV infection. The modes of transmission and genotypes of HEV in FG remain uncertain.

To estimate the prevalence of hepatitis E virus (HEV) infection by the presence of anti-HEV IgG antibodies in Latin America and the Caribbean (LAC).

Systematic review and meta-analysis.

Systematic searches were conducted in the Medline, Lilacs and Embase databases, selecting 81 studies comprising 38,951 individuals in accordance with the PRISMA Statement. Analyses were performed by using the random-effects model. Data analysis considered study cohort and geographic location.

The prevalence of hepatitis E in LAC ranged from 0 % to 36 % and the overall prevalence was 9.0 %, with important heterogeneity (I2 = 97.3 %). Meta-analysis of subgroups showed prevalence of hepatitis E of 9.0 % in the general population, 6.0 % in blood donors, 9.0 % in rural population, 21.0 % in occupational exposure to pigs, 9.0 % in pregnant women, 7.0 % in immunocompromised individuals, 12.0 % in individuals with chronic liver disease and 9.0 % in individuals with acute hepatitis. According to geographic location, the prevalence of hepatitis E was 7.0 % in Argentina, 16.0 % in Bolivia, 7.0 % in Brazil, 17.0 % in Colombia and 24.0 % in Cuba. The generated funnel plot appeared asymmetric, with evidence of bias according to Egger (p = 0.000) and Begg (p = 0.003) tests. In the analysis, which included only studies with a quality score >5, the prevalence of hepatitis E was 8.0 %. When analysing studies with sample sizes greater than 200 and 500, we identified prevalences of 8.0 % and 7.0 %, respectively.

The information obtained in this review warns about the current consolidated prevalence of hepatitis E in LAC, which can be a tool for planning prevention strategies.

The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal-oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection.

Viral hepatitis remains a global health challenge and immune status affects outcomes. In patients with haematological malignancies, including haematopoietic stem-cell transplantation recipients, viral hepatitis can be life-threatening due to the direct effects of the virus or the need to modify or delay chemotherapy. Additionally, haematopoietic stem-cell donors with past or current viral hepatitis infections might transmit the virus to recipients. The growing recognition of hepatitis E virus (HEV), advances in haematological therapies, and the availability of direct-acting antivirals for hepatitis C virus (HCV), led the 2022 9th European Conference on Infections in Leukaemia (ECIL-9) to update the 2013 ECIL-5 guidelines on viral hepatitis. The ECIL organising committee convened a panel of 13 impartial international experts (all authors of this Review) in viral hepatitis, both within and outside the fields of haematological malignancies and immunosuppression. The ECIL-9 panel conducted a review of the literature on hepatitis B virus (HBV), HCV, and HEV, grading the evidence based on the European Society for Clinical Microbiology and Infectious Diseases system. The panel identified key clinical questions and outcomes and built on the recommendations established during ECIL-5. A consensus conference was held in Sofia Antipolis, France, from Sept 15-17, 2022, bringing together 49 experts from 19 countries. The ECIL-9 panel presented the proposed recommendations, which were revised following expert discussions. A final consensus on updated guidelines was reached in a second plenary session. The updated ECIL-9 guidelines provide evidence-based recommendations on the prevention, screening, treatment, and long-term surveillance of viral hepatitis in patients with haematological malignancies and haematopoietic cell transplantation recipients.

Chronic hepatitis E virus (HEV) infection, which primarily affects the immunocompromised, can rapidly progress to liver fibrosis and cirrhosis if untreated. However, current therapeutic options are extremely limited and have significant adverse effects. Over the past decade, virus-specific T-cell therapy has shown promise as an alternative safe and effective treatment strategy for other refractory viral infections such as cytomegalovirus, adenovirus, and polyomavirus infections in hematopoietic stem cell and solid organ transplant recipients. Given the key role of T lymphocytes in the control of HEV replication and the fact that HEV-specific T-cell responses are typically diminished in immunosuppressed patients with persistent HEV infection, adoptive immunotherapy with HEV-specific T cells could serve as a novel addition to the HEV treatment repertoire, which is in dire need of expansion.

Genetic disorders affecting hepatobiliary transporters can be triggered by various factors, resulting in marked cholestasis.

We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection. Following an extensive clinical examination that ruled out common causes of cholestatic liver damage, we conducted next-generation sequencing to determine the genetic profiles of the patients. The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation, including ATP8B1, ABCB11, ABCB4, MYO5B, and FXR. For a comprehensive understanding of the pathophysiology, we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact. Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.

Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis, and we categorize the significance of the various genetic variants based on the current state of research.

Hepatitis E virus (HEV) infection causes acute hepatitis, chronic hepatitis, particularly in compromised hosts, and various extrahepatic manifestations. HEV infection is reportedly associated with biliary-pancreatic diseases, such as gallstones, cholangitis, choledocholithiasis, and acute pancreatitis. Severe jaundice and prolonged cholestasis are also atypical manifestations of HEV infection. The mechanism and genes involved in cholestasis, namely sinusoidal uptake of blood, bile salt synthesis and secretion from hepatocytes to the canaliculus, have been elucidated. HEV infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1, adenosine triphosphate-binding cassette (ABC) protein B4, ABCB11, Myosin VB, and/or farnesoid X receptor (FXR/NR1H4). Although prolonged cholestasis associated with these gene mutations does not seem to be specific to HEV infection, these mutations may be risk factors related to the severity of HEV infection. The use of the pregnane X receptor agonist rifampicin and the peroxisome proliferator-activated receptor activator bezafibrate may be useful for the treatment of cholestasis. These studies provide new insights into understanding the mechanisms of severe jaundice and prolonged cholestasis caused by HEV infection.

Hepatitis E virus (HEV), the causative agent of hepatitis E, is the leading cause of acute viral hepatitis worldwide; under immunosuppression, infection can lead to chronic liver disease. Furthermore, extrahepatic manifestations, particularly renal manifestations, are frequently associated with infection. This is important considering the global burden of chronic kidney disease (CKD). However, the study of chronic hepatitis E has been limited to liver disease, and its definition with respect to renal disease is still incomplete. Recently, through a protocol aimed at identifying HEV seroprevalence in a cohort of patients on hemodialysis, we incidentally identified HEV RNA in a patient with a history of alcoholism, diabetes mellitus, and essential systemic hypertension. In this study, we aimed to follow up this case to characterize hepatitis E in the context of CKD. Notably, we identified the development of chronic HEV genotype 3 infection without seroconversion or evidence of liver damage. Moreover, apparent immunocompetence was identified in the patient. Considering that HEV is still neglected in numerous countries and that it is not included in the differential diagnosis of kidney disease, our findings support the need to consider HEV infection in patients with renal disease, even in the absence of liver deterioration.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis globally. HEV infections can progress to chronic disease in immunocompromised individuals and may also cause extrahepatic complications. By contrast to other hepatitis viruses, HEV exhibits a broad tissue tropism, and certain genotypes have the ability to infect multiple species. The initial steps of surface attachment and host cell entry are critical steps in the viral infection cycle and serve as key determinants to establish an infection. This review summarizes the current understanding of HEV entry, focusing on molecular entry factors, such as viral receptors, and discusses differences between quasi-enveloped and non-enveloped HEV. We further cover recent developments of assay systems to study HEV entry and highlight experimental strategies to identify novel host components required for HEV entry. Advancing our understanding in these areas could help to guide the development of targeted antiviral strategies to block the early stages of HEV infection.

Hepatitis E Virus (HEV) has gained public health attention as one of the causative agents of viral hepatitis. Our study aimed to provide data about HEV seropositivity in the Israeli general population, including its seroprevalence geographical distribution, and to identify variables as possible risk factors for HEV exposure. A seroprevalence cross-sectional study was conducted: HEV serological status was determined in 716 blood samples collected from the routine check-up blood samples. Demographic information was available for all samples. The overall prevalence of HEV IgG in an apparently healthy population in the north of Israel was 10.5%, with no evidence of positive HEV IgM. There was a significant association between HEV seropositivity and elderly age and low socioeconomic status (SES). The age-adjusted seroprevalence was significantly lower among Jews compared to Arabs with a rate ratio of 2.02. We identified clusters (hot spots) of HEV infection in three regions under study. Our results confirmed a high prevalence of anti-HEV in the country where clinical hepatitis E is not endemic. For the first time, this study showed that a hot spot analysis was able to provide new knowledge about actual exposure zones. As HEV infection is not a notifiable disease, it is probably underdiagnosed. Thus, better awareness among physicians is warranted.

Hepatitis E virus (HEV) is a zoonotic pathogen with multiple hosts, posing significant public health risks, especially in regions like Japan where game meat consumption is prevalent. This study investigated HEV infection and viral shedding in wild boars, sika deer, and Japanese serows across Japan. A total of 1896 serum samples were tested for anti-HEV antibodies, 1034 for HEV RNA, and 473 fecal samples for viral shedding. Anti-HEV antibodies were detected in wild boars from all seven prefectures studied, while HEV RNA was detected in wild boars from Fukuoka, Oita, and Miyazaki in southern Japan, as well as Yamaguchi prefecture. Genetic analysis revealed subtypes 3b, 4a, and 4g, with 3b being the most prevalent. Subtype 3b exhibited distinct geographical clustering, whereas 4g persisted exclusively in Yamaguchi for over 12 years. Infectious HEV particles were confirmed in wild boar feces, highlighting the risk of environmental contamination and zoonotic transmission. Sika deer showed no evidence of HEV infection, and only one Japanese serow tested positive for antibodies without detectable RNA. These findings underscore the importance of ongoing surveillance to assess the zoonotic risks from game meat consumption and prevention of HEV transmission to humans.

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%.

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.

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) is a major cause of acute hepatitis. HEV genotypes 1 and 2 are associated with oro-faecal epidemics and fulminant hepatitis in pregnant women. HEV genotypes 3 and 4 are a zoonosis transmitted by uncooked pork. Infection is usually spontaneously resolutive. Chronic hepatitis may occur in immunocompromised patients. Extrahepatic disease is also possible. Prevention is based on hygiene, especially in high-risk patients, and access to safe drinking water for all. A recombinant vaccine against HEV has been developed and is currently being validated by the WHO.

Hepatitis E virus (HEV) infection can become chronic in immunocompromised patients, like solid organ transplant recipients (SOTRs). We evaluated HEV prevalence, risk factors, and outcomes among SOTRs in a hyperendemic HEV area. Three hundred SOTRs were enrolled from April to July 2019 and tested for anti-HEV IgM and IgG and HEV RNA. Sixty-three recipients (21%) were positive for any HEV marker. HEV infection was independently associated with older age and pork liver sausage consumption. Three viremic recipients harbored genotype 3e and 3f according to HEV RNA sequencing and phylogenetic analysis. Overall, 10 recipients had markers of active/recent infection (HEV RNA and/or anti-HEV IgM) and were followed up prospectively. Five of them spontaneously resolved their HEV infection. In two recipients, HEV clearance was achieved only through immunosuppression reduction, while three needed ribavirin therapy to achieve virologic resolution. We observed a chronic course in 30% of SOTRs with active/recent HEV infection. No association was found between tacrolimus assumption and chronicization. In conclusion, we found a high prevalence of infection among SOTRs attending a transplant center in a hyperendemic Italian HEV region. Systematic screening for all HEV markers and dietary education for infection control are needed for transplant recipients.

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.

Hepatitis E virus (HEV) is one of the leading causes of acute hepatitis, with immunosuppressed individuals, such as oncology patients, being particularly vulnerable to chronic infections that may progress to liver disease or fatal outcomes. Assay variability complicates HEV prevalence assessment in at-risk groups. This study aimed to compare the reliability and concordance of three HEV antibody assays-Wantai, Euroimmun, and Elecsys®-in immunosuppressed oncology patients.

In this prospective pilot study, serum samples were obtained from oncology patients between September 2020 and October 2021. Samples were collected both at baseline (treatment-naive) and during ongoing treatment. A healthy control group was retrospectively included for comparative analysis. Anti-HEV IgM and IgG antibodies were tested in all samples using enzyme-linked immunosorbent assays (Wantai, Euroimmun) and an electrochemiluminescence immunoassay (Elecsys®). Demographic and clinical data, along with information on HEV risk factors, were extracted from medical records and patient questionnaires.

HEV IgM prevalence ranged from 0% (Wantai) to 6% (Elecsys®), while IgG prevalence was 12% (Euroimmun), 38% (Wantai), and 53% (Elecsys®). Concordance was poor, with Cohen's Kappa values indicating slight to moderate agreement (κ = 0.000-0.553). Patients with hematological malignancies exhibited the highest IgG seroprevalence. Risk factor analysis revealed the highest association between HEV exposure and the consumption of undercooked pork or crop-based agriculture.

Significant variability among HEV serological assays highlights the challenges of reliable HEV diagnostics in immunosuppressed oncology patients. Assay selection and improved testing strategies are critical for this high-risk group.

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.

Our objective was to evaluate the shifting burden of hepatitis E virus (HEV) across age groups and geographical scopes from 1990 to 2021 and to predict incidence rates for 2030. Leveraging data from the Global Burden of Diseases 2021, we examined HEV incidence and disability-adjusted life years, calculated average annual percentage changes (AAPCs) and identified pivotal years for incidence trends. We stratified our analysis by age, sex, and sociodemographic index and employed the Bayesian age-period-cohort model to predict future incidence. HEV incidence decreased from 269.68 per 100,000 in 1990 to 260.41 per 100,000 in 2021, with an AAPC of -0.1. Notably, the incidence significantly decreased in 1995, 2006, 2009, and 2014. Southern sub-Saharan Africa presented the most notable increase in HEV infection incidence, increasing from 218.59 per 100,000 individuals (95% [UI] 181.36 to 262.28) to 232.25 per 100,000 individuals (191.9 to 279.82), with an AAPC of 0.2 (95% [CI] 0.2 to 0.2). The 2030 incidence is projected to be 267.44 per 100,000 (95% UI, 235.27 to 299.6). Despite a general decline in HEV incidence associated with health interventions, some regions still report annual increases, underscoring the need for intensified disease management to meet the 2030 goals.

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.

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.

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 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.