Search Results (168)

Hepatitis E virus (HEV) is a pathogen that has caused various epidemics and sporadic localized cases. It is considered to be a public health problem worldwide. HEV is a small RNA virus with a significant genetic diversity, a broad host range, and a heterogeneous geographical distribution. HEV is mainly transmitted via the faecal–oral route. However, some animals are considered to be natural or potential reservoirs of HEV, thus elucidating the zoonotic route of transmission via the environment through contact with these animals or consumption of their by-products. Other routes of human-to-human transmission are not negligible. The various human–animal–environment entities, taken under one health approach, show the circulation and involvement of the different species (mainly Paslahepevirus balayani and Rocahepevirus ratti) and genotypes in the spreading of HEV infection. Regarding P. balayani, eight genotypes have been described, of which five genotypes (HEV-1 to 4 and HEV-7) are known to infect humans, while six have been reported to infect animals (HEV-3 to HEV-8). Furthermore, the C1 genotype of the rat HEV strain (HEV-C1) is known to be more frequently involved in human infections than the HEV-C2 genotype, which is known to infect mainly ferrets and minks. Contamination can occur during run-off, flooding, and poor sanitation, resulting in all of these genotypes being disseminated in the environment, contaminating both humans and animals. This systematic review followed the PRISMA guidelines and was registered in PROSPERO 2025 CRD420251071192. This research highlights the importance of investigating the transmission routes and major circulating HEV genotypes in order to adopt a holistic approach for controlling its emergence and preventing future outbreaks. In addition, this article outlines the knowledge of HEV in Africa, underlining the absence of large-scale studies at the environmental, human, and animal levels, which could improve HEV surveillance on the continent. Full article

Hepatitis E virus (HEV) causes significant morbidity and mortality globally, particularly affecting vulnerable populations such as pregnant women. HEV239 (Hecolin^®), a recombinant vaccine containing the immunodominant protruding (E2) domain of the HEV capsid protein, has demonstrated effectiveness, yet detailed human cellular immune responses remain understudied. This study characterized humoral and cellular immune responses following vaccination with HEV239 or natural HEV infection in healthy Bangladeshi women aged 16–39 years. Using dual IFNγ and IL-4 ELISpot assays, we found robust, predominantly Th1-mediated cellular responses at 30 days after the third vaccine dose, comparable to responses during acute infection. Longitudinal antibody assessments confirmed sustained antibody production, primarily against the E2 domain of genotypes 1 and 3, persisting up to two years post-vaccination. Despite limitations related to sample size and assay sensitivity, our findings underscore the immunogenic potential of HEV239 and support a broader use in HEV-endemic regions. Full article

Paslahepevirus balayani (hepatitis E virus), a zoonotic pathogen transmitted primarily via the fecal–oral route, has undergone shifting transmission dynamics in China, with foodborne and zoonotic routes becoming increasingly significant. To assess the potential risk of HEV transmission through dairy products, this study investigated HEV RNA presence in raw milk from cows, sheep, and goats in Hebei Province, China. From March 2024 to April 2025, we collected 102 cow milk, 18 sheep milk, and 59 goat milk samples, analyzing them using RT-qPCR, with positive samples confirmed by RT-Nested PCR and partial ORF2 sequencing. While no HEV RNA was detected in cow milk, 3/18 (16.67%) sheep milk and 1/59 (1.69%) goat milk samples tested positive. Phylogenetic analysis of two sheep-derived and one goat-derived HEV isolate showed 99.43–100% nucleotide identity to local swine HEV strains (HEV/HB-SJZ158/CHN/2021 and HEV/HB-CD28/CHN/2021), all clustering within genotype 4d, the dominant subtype in the region. This study provided the first evidence of HEV RNA in sheep and goat milk in Hebei Province, suggesting possible cross-species transmission from pigs to ruminants. These findings highlighted the need for further research on HEV transmission risks through dairy products and emphasize the importance of monitoring zoonotic HEV strains in food safety assessments. Full article

Hepatitis E, caused by the hepatitis E virus (HEV), is a zoonotic disease that extends beyond hepatocellular necrosis to replicate in multiple organs. While most infections are self-limiting, HEV infection during pregnancy is associated with severe outcomes, including acute liver failure, preterm delivery, and miscarriage, with the mechanisms underlying this high pathogenicity remaining poorly understood. This study established a pregnant tree shrew model with a late-stage HEV infection and a cellular model using zoonotic HEV genotypes GT3 and GT4 to investigate the effects of estrogen on HEV replication. Results showed that negative-strand RNA detection revealed replicative intermediates in feces and tissues during the acute phase, with peak viral loads occurring within one week and the highest titers in bile. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels rose at 3 days post-inoculation (DPI), peaking at 7 DPI. Elevated estrogen levels post-miscarriage correlated with increased viral loads, a trend mirrored in cell culture models showing linear relationships between estrogen and viral replication. Histopathology demonstrated viral hepatitis lesions in liver tissues and abnormalities in the uterus, ovaries, and brain, including hydropic degeneration, neuronal disruption, and granulosa cell necrosis. This study developed a pregnant tree shrew model for HEV infection, providing a robust tool for exploring pathogenic mechanisms during pregnancy and genotype-specific differences in zoonotic HEV pathogenicity. These findings offer new insights into the role of estrogen in HEV replication and its contribution to adverse pregnancy outcomes. Full article

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. Full article

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. Full article

This study reports an outbreak of hepatitis-splenomegaly syndrome (HSS) in a color broiler parent stock flock in Bangladesh, marking the first known instance of HSS associated with avian hepatitis E virus (aHEV) genotype 7 outside Europe and only the second report of HSS in South Asia. The affected flock exhibited severe clinical signs, including a high cumulative mortality, reaching 31.6% in hens, and an abrupt decrease in egg production, dropping by over 20 percent. Histopathological analysis of liver and spleen samples revealed multifocal areas of necrosis, hemorrhages, and bacterial colonies. RT-PCR confirmed the presence of aHEV and immunohistochemistry showed signals within hepatic sinusoids and peri-ellipsoidal zones in the spleen. Complete genome sequencing of RNA from liver and bile samples on the Illumina platform established a pathogenic link to aHEV genotype 7. Despite aHEV’s known association with HSS, inconsistencies in disease manifestation suggest additional cofactors influencing pathogenesis, with secondary bacterial infections potentially contributing to clinical severity in this outbreak. Overall, this case expands the geographic distribution of aHEV genotype 7 and highlights the need for further epidemiological studies to investigate genotype–pathogenicity associations, especially in regions with limited prior data on HSS. Full article

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. Full article

Hepatitis E virus (HEV) is one of the most common pathogens causing acute hepatitis. Rat HEV, a member of the genus Rocahepevirus, infects mainly rat but can also cause human zoonotic infection. A survey of the virome of rats via next-generation sequencing (NGS) was performed in Yunnan Province and Inner Mongolia in China. Further screening of rat HEV was conducted by nested PCR. The complete genome of six representative strains were obtained by NGS and RT-PCR. The virome analysis revealed that multiple reads were annotated as Hepeviridae. The screening results showed that HEV was detected in 9.6% (34 of 355) of the rat samples and phylogenetically classified into three lineages. The sequences from Yunnan clustered with Rocahepevirus ratti, named the YnRHEV group, and those from Inner Mongolia were separated into two lineages, named the NmRHEV-1 and NmRHEV-2 groups. Complete sequence analysis showed that YnRHEV had very high sequence identity to a human HEV strain identified in immunosuppressed patients (88.7% to 94.3%), a reminder of the risk of cross-species transmission of rodent HEV. Notably, NmRHEV-1 and the most closely related rat HEV, RtCb-HEV/HeB2014, were divergent from other HEV. The phylogenetic analyses and lower sequence identities of the complete genome suggested the NmRHEV-1 to be a novel putative genus of the subfamily Orthohepevirinae. NmRHEV-2 shared the highest sequence identities (70.6% to 72.0%) with the species Rocahepevirus eothenomi, which may represent a putative novel genotype. This study revealed high genetic diversity of Hepeviridae in rats in China and a potentially zoonotic Rocahepevirus ratti strain. Full article

Hepatitis E viruses (HEV) cause hepatitis E in humans. In industrialized countries, sporadic HEV infections, typically caused by HEV genotypes 3 or 4, can become chronic and progress to liver cirrhosis in immunocompromised individuals. Pigs are a significant animal reservoir, implicating raw or undercooked pork products as potential sources of human infection. To better understand HEV dissemination in the Belgian pig population, potential risk factors were investigated by linking farm-level HEV serological status to biosecurity questionnaire data. Farrow-to-finish herd type, free-range systems, and poor boot hygiene were significantly associated with higher within-herd prevalences. This enabled an initial risk profiling of various farming types and the development of predictions for all Belgian pig farms. When combined with the census of the Belgian wild boar population, the predicted HEV status of all professional Belgian pig farms (based on these associations) does not suggest that the proximity of wild boars is a main source of HEV in free-ranging herds. Identifying risk factors for increased circulation of HEV between and within pig farms is critical to controlling its spread and reducing human infection. Full article

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E infection in humans. Two epidemiological patterns of the disease exist—endemic and sporadic. Genotypes 1 (HEV-1) and 2 (HEV-2) are transmitted through contaminated water and are responsible for the outbreaks of many large-scale epidemics in developing countries of Asia and Africa. Genotypes 3 (HEV-3) and 4 (HEV-4) have zoonotic potential and cause sporadic cases and small outbreaks in high-income countries. The first case of HEV infection in swine was confirmed in 1997 and later detected in other animal species. The aim of this study was to investigate the seroprevalence of HEV infection in pig farms in Vojvodina province, Serbia. Three hundred blood samples were collected from five different categories of pigs from 3 different farms on the territory of the South Bačka district in Vojvodina (Serbia). The analyses were conducted by in-house ELISA, while the western blot method was used as a confirmatory test for doubtful results. The presence of HEV IgG was detected on all three examined farms. The established seroprevalence in Farm A was 37%, 31% in Farm B, and 54% in Farm C. The mean seroprevalence for all farms was 40.66%. A higher seroprevalence was found in fatteners compared to younger categories of pigs. We concluded that HEV is widespread on pig farms with intensive management. Further analyses should be conducted with the aim of implementing a surveillance program to prevent possible human infection. Full article

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients’ ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood–testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men. Full article

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. Full article

The hepatitis E virus (HEV) is an emerging infectious disease with zoonotic potential, causing acute hepatitis in humans. Infections in healthy individuals are often acute, self-limiting and asymptomatic, thus leading to the underdiagnosis of HEV infections. Asymptomatic HEV infections pose a problem for blood transfusion safety by increasing the risk for transfusion-transmitted HEV infections. Here, we describe the journey from determining the HEV seroprevalence among blood donors to the implementation of routine HEV RNA testing of all blood products in Switzerland in 2018 and summarise the HEV cases detected since. In total, 290 HEV-positive blood donations were detected by mini-pool nucleic acid testing (NAT) in Switzerland in the period of October 2018–December 2023, equal to an incidence of 20.7 per 100,000 donations. Thanks to the implemented scheme, no transfusion-transmitted infections occurred in this period. Furthermore, blood donation monitoring has proven to be an effective means of detecting HEV outbreaks in the general population. HEV cases in Swiss blood donors are caused by two major genotypes, the Swiss-endemic subtypes 3h3 and 3c. Interestingly, 11 HEV cases (5%) were of genotype 3ra, a variant found in wild and farmed rabbits. Our results indicate that mini-pool NAT is an efficient method to reduce the risk of transfusion-transmitted HEV infections. Full article

Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections. To investigate whether gerbils can be used as animal models for other subtypes of HEV-3, we injected gerbils with five HEV-3 subtypes (HEV-3b, -3e, -3f, -3k, and -3ra) and compared the infectivity of the subtypes. We detected viral RNA in the gerbils’ feces. High titers of anti-HEV IgG antibodies in serum were induced in all HEV-3b/ch-, HEV-3f-, and HEV-3e-injected gerbils. Especially, the HEV-3e-injected animals released high levels of viruses into their feces for an extended period. The virus replication was limited in the HEV-3b/wb-injected and HEV-3k-injected groups. Although viral RNA was detected in HEV-3ra-injected gerbils, the copy numbers in fecal specimens were low; no antibodies were detected in the sera. These results indicate that although HEV-3′s infectivity in gerbils depends on the subtype and strain, Mongolian gerbils have potential as a small-animal model for HEV-3. A further comparison of HEV-3e with different genotype strains (HEV-4i and HEV-5) and different genera (rat HEV) revealed different ALT elevations among the strains, and liver damage occurred in HEV-4i- and HEV-5-infected but not HEV-3e- or rat HEV-infected gerbils, demonstrating variable pathogenicity across HEVs from different genera and genotypes in Mongolian gerbils. HEV-4i- and HEV-5-infected Mongolian gerbils might be candidate animal models to examine HEV’s pathogenicity. Full article