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To further investigate the prevalence of hepatitis E virus (HEV) infection and characterize HEV genomes among Japanese wild boars (Sus scrofa leucomystax), 1880 boars captured in 17 prefectures in Japan from 2013 to 2019 were studied. Overall, anti-HEV IgG was detected in 8.9 % and HEV RNA was detected in 3.9 % of boars, which was comparable with our previous studies during 2003-2013 (10.3 % and 3.5 %, respectively). Among 74 boar HEV strains obtained from infected boars in the present study, 50 (68 %) were classified into genotype 3 (3a and 3b), 23 (31 %) were classified into genotype 4 (4i), and the remaining strain (wbJGF_19-1) was classified into genotype 5. The wbGF_19-1 strain shared 92.7 % identity over the entire genome with the prototype genotype 5 strain (JBOAR135-Shiz09). The identification of the second genotype 5 HEV strain in a place that is located only 100 km from the site at which JBOAR135-Shiz09 was identified, suggests that genotype 5 HEV circulates within a relatively close range in Japan. Genetically similar HEV strains forming a clade were identified from wild boars living in each area during the observation period of 11-13 years, although the nucleotide sequence changed gradually, accounting for up to 3.4-3.6 % within the 412-nucleotide ORF2 sequence. Eight groups of boars with a cluster of HEV infections were observed, consisting of two, three or four infected offspring, presumably born to the same mother or offspring with their mother. These results suggest that wild boars continue to be important reservoirs for HEV infection in humans in Japan., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV belongs to the Hepeviridae family and at least five genotypes (gt) infect humans. Several animal species are reservoirs for different HEV strains, and they are the source of infection for humans. Some HEV strains are species specific, but other strains could cross species and infect many hosts. The study of HEV infection and pathogenesis was hampered due to the lack of an in vitro and in vivo robust model system. The cell culture system has been established for certain HEV strains, especially gt3 and 4, but gt1 strains replicate poorly in vitro. To date, animal models are the best tool for studying HEV infection. Non-human primates (NHPs) and pigs are the main animal models used for studying HEV infection, but ethical and financial concerns restrict the use of NHPs in research. Therefore, new small animal models have been developed which help more progress in HEV research. In this review, we give updates on the animal models used for studying HEV infection, focusing on the applicability of each model in studying different HEV infections, cross-species infection, virus-host interaction, evaluation of anti-HEV therapies and testing potential HEV vaccines., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is an emerging zoonosis caused by a positive RNA single stranded virus of the Hepeviridae family. In developed countries, pigs and wild boars are the main reservoir for zoonotic genotypes 3 and 4. In spring 2017, for the first time HEV was detected in wild boars captured in the Regional Park of the Euganean Hills, in north-eastern Italy. Phylogenetic analysis of two complete viral genomes and seven partial ORF1 and ORF2 sequences of HEV viruses, selected from twelve positive animals, showed that the viruses grouped together within genotype 3 but clustered separately from previously identified subtypes, thus suggesting the identification of a novel genotype 3 subtype. The phylogenetic analysis of nine partial ORF2 sequences showed the closest similarity with wild boar/human viruses identified in central-northern Italy in 2012. The circulation of HEVs in this area, characterized by a vast man-made environment, an overpopulation of wild boars and >150 swine farms, should be considered in a public health perspective. Further investigations at the wild/domestic species and human interface are therefore necessary to gain a deeper understanding of HEV dynamics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is an important pathogen causing public health burden. Swine has been recognized as a main reservoir. Interestingly, genotype 1 HEV only infects human; whereas genotype 3 and 4 are zoonotic. However, there is a lack of in-depth understanding in respect to the transmission from swine to human. Codon usage patterns generally participate in viral survival and fitness towards its hosts. We have analyzed codon usage patterns of the three open reading frames (ORFs) for 243 full-length genomes of HEV genotypes 1, 3 and 4. The divergence of synonymous codon usage patterns is different in each ORF for genotypes 1, 3 and 4, but the genotype-specific codon usage bias in genotype 1 is stronger than those of genotypes 3 and 4. In respect to genotypes 3 and 4, compared with strains isolated from human, HEV isolated from swine shows appreciable variation in adaptation of codon usages to human or swine. These results may help to understand the transmission and host adaptation of HEV genotypes 3 and 4 from swine to human., (Copyright © 2018. Published by Elsevier B.V.)

Background: Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis worldwide. Typically associated with a self-limiting illness, infection may persist in immunosuppressed populations with significant morbidity and mortality. Based on clinical data published world-wide, UK blood safety guidance recommends the universal screening for HEV RNA of blood donors and donors of tissue, organs and stem cells., Objectives: This cross-sectional study aimed to determine the point prevalence of HEV viraemia and clinical course of viraemic patients in the peri-transplant period in solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) recipients transplanted over a 3-year period (2013-2015)., Study Design: Nucleic acid extracts of whole blood from patients undergoing SOT or HSCT were tested by an in-house real-time reverse-transcriptase polymerase chain reaction assay for HEV RNA. Samples were tested at baseline (time of transplant), 30, 60 and 90 days post-transplant., Results: 870 patients (259 HSCT, 262 liver and 349 kidney transplant) were included with 2554 samples meeting the inclusion criteria. No kidney transplant patients had HEV viraemia at time of testing. One HSCT and three liver transplant patients were found to be HEV RNA positive. Overall this represented 0.46% of the patients testing positive for HEV viraemia., Conclusions: Prevalence of HEV viraemia in SOT and HSCT patients in U.K. although higher than in the general population is low at baseline and remains low throughout the early post-transplant phase. Clearance of viraemia can be maintained despite ongoing immunosuppression. Prospective U.K. studies are necessary to inform screening policies in this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60% of immunocompromised patients infected with HEV genotype 3. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Hepatitis E virus (HEV), family Hepeviridae, has raised considerable public health concerns because of its zoonotic potential; however, the animal to animal transmissions and the natural chain of hepevirus infections in wildlife are less known. Using random amplification and next generation sequencing technology a novel HEV in birds of prey was serendipitously identified in Hungary. HEV RNA was detected in total of 2 (18%) of the 11 and 1 (14%) of the 7 faecal samples from common kestrels and red-footed falcons, respectively. High faecal viral load (2.03×10(8) genomic copies/ml) measured by qPCR. The complete genome of strain kestrel/MR22/2014/HUN (KU670940) HEV is 7033-nt long including a 35-nt 5'end and a 63-nt 3'end (excluding the poly(A)-tail). Sequence analyses indicated that the ORF1 (4920nt/639 aa), ORF2 (1989nt/662 aa) and ORF3 (360nt/119aa) proteins of kestrel/MR22/2014/HUN shared the highest identity (58.1%, 66.8% and 28.5%) to the corresponding proteins of ferret, rat and human genotype 4 Orthohepeviruses, respectively. Interestingly, the ORF3 protein is potentially initiated with leucine (L) using an alternate, non-AUG (UUG) start codon. This study reports the identification and complete genome characterization of a novel Orthohepevirus species related to mammalian HEVs in birds of prey. It is important to recognize all potential hosts, reservoirs and spreaders in nature and to reconstruct the phylogenetic history of hepeviruses., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: The risk assessment for blood transfusion is an essential step that must precede any screening strategy of a pathogen transmitted by transfusion. After several cases of HEV transmission by transfusion in France, a risk assessment for this virus was performed., Methods: We used a method based on the prevalence of HEV-RNA in plasmas collected for the preparation of SD-plasma. To estimate the rate of HEV-RNA positive among all blood donations, data on SD-plasma were adjusted on the following HEV risk factors: gender, age group and region of residence. We assumed that HEV risk factors were the same in plasma donors and whole blood donors., Results: Among 57,101 plasma donations tested for HEV-RNA in 2013, 24 were positive (crude rate of 4.2 per 10,000 donations). After adjustment, the total number of HEV-RNA positive blood donations was estimated at 788, accounting for a rate of 2.65 per 10,000 donations (95% CI: 1.6-3.7) or 1 in 3800 donations (1 in 6,200-1 in 2,700). This rate was 12 times higher in men than in women, increased with age, and varied according to region of residence., Conclusion: The risk of blood donation contamination by HEV has been estimated to be 1 in 3800 donations in 2013. An essential input is still missing to assess now the risk in recipients: the minimum infectious dose. Furthermore, the risk in recipients has to be analyzed according to characteristics of transfused patients: presence of anti-HEV immunity, existence of chronic liver disease or immunodeficiency., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The hepatitis E virus (HEV) was first identified in 1990, although hepatitis E-like diseases in humans have been recorded for a long time dating back to the 18th century. The HEV genotypes 1-4 have been subsequently detected in human hepatitis E cases with different geographical distribution and different modes of transmission. Genotypes 3 and 4 have been identified in parallel in pigs, wild boars and other animal species and their zoonotic potential has been confirmed. Until 2010, these genotypes along with avian HEV strains infecting chicken were the only known representatives of the family Hepeviridae. Thereafter, additional HEV-related viruses have been detected in wild boars, distinct HEV-like viruses were identified in rats, rabbit, ferret, mink, fox, bats and moose, and a distantly related agent was described from closely related salmonid fish. This review summarizes the characteristics of the so far known HEV-like viruses, their phylogenetic relationship, host association and proposed involvement in diseases. Based on the reviewed knowledge, a suggestion for a new taxonomic grouping scheme of the viruses within the family Hepeviridae is presented., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Hepatitis E virus is classified into four genotypes that have different geographical and host distributions. The main cause of sporadic autochthonous type E acute hepatitis in developed countries is genotype 3, which has a worldwide distribution and widely infects pigs. The aim of this study was to make hypotheses concerning the origin and global dispersion routes of this genotype by reconstructing the spatial and temporal dynamics of 208 HEV genotype 3 ORF-2 sequences (retrieved from public databases) isolated in different geographical areas. The evolutionary rates, time of the most recent common ancestors (tMRCAs), epidemic growth and phylogeography of HEV-3 were co-estimated using a MCMC Bayesian method. The maximum clade credibility tree showed the existence of two distinct main clades: clade A, which consists of only European subtypes (HEV-3e and 3f), and clade B, which consists of European subtype 3c and all of the Asian subtypes (3a, 3b and 3d) sharing a common ancestor, which most probably existed in Asia in 1920s. All of the North American isolates belonged to Asian subtype 3a. On the basis of our time-scaled phylogeographical reconstruction, we hypothesise that after originating in the early 1800s in Europe, HEV reached Asia in the first decades of 1900, and then moved to America probably in the 1970s-1980s. Analysis of the skyline plot showed a sharp increase of the number of infections between the 1980s and 2005, thus suggesting the intervention of new and highly efficient routes of transmission possibly related to changes in the pig industry., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ∼70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74-93% and 63-87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4., (Published by Elsevier B.V.)

Hepatitis E is an important public health problem in many countries. However, there is no definite conclusion about the zoonotic reservoir, transmission patterns and risk factors of hepatitis E in the human population. The aim of this study was to analyze the epidemiological and viral genotype characteristics of hepatitis E cases in northern China. Surveillance was conducted in two hospitals in Liaoning and Hebei province from July 2010 to June 2012. Out of a total of 116 diagnosed patients, 88 (75.9%) were male and 28 (24.1%) were female and most (73%) were in the age group 40-70 years. In both hospitals, cases were diagnosed more frequently in March than in other months. HEV RNA was amplified from 41 patients and characterized by nucleotide sequencing and phylogenetic analysis. Most of the isolates (37 strains, 90.3%) were genotype 4, including subgenotypes 4a, 4b, 4d, 4h, 4i and a new subgenotype. One subgenotype 3a strain was isolated from Baoding, Hebei province. Three genotype 1b strains were found from patients in Jinzhou, Liaoning province. Most of the genotype 4 strains and the genotype 3 strains were phylogenetically related to known swine isolates. In conclusion, the finding that HEV infects mostly middle-aged and elderly men and that the incidence spiked in March may reflect the zoonotic transmission characteristics of HEV infection. Pigs, but not rabbits, were the important reservoirs in this area, because genotype 4 HEV was found to be responsible for the majority hepatitis E cases. However, genotype 1 is still present in northern China. Also, the first isolation of genotype 3 HEV in this area indicates that alternative routes of HEV transmission might exist., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Hepatitis E virus strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. Further issues remain to be clarified, including whether the genotype of rabbit HEV differs from human and swine HEV genotype 3 and whether rabbit HEV can infect human and other animals. HEV was found in farmed rabbits in several geographic areas of China, in USA and more recently in France. The prevalence of antibodies against HEV was 36%, 57% and 55% in rabbits from Virginia (USA), Gansu Province and Beijing (China), respectively. HEV RNA was detected in 16.5% of serum samples from farmed rabbits in Virginia, 7.5% in Gansu Province and 7.0% in Beijing. HEV RNA was detected in 7% of bile samples from farmed rabbits and in 23% of liver samples from wild rabbits in France. The full-length genomic sequences analysis indicates that all the rabbit strains belong to the same clade. Nucleotide sequences were 72.2-78.2% identical to HEV genotypes 1-4. Comparison with HEV sequences of human strains circulating in France and reference sequences identified a human strain closely related to rabbit HEV. A 93-nucleotide insertion in the X domain of the ORF1 of the human strain and in all the rabbit HEV strains was found. Moreover, the ability of rabbit HEV to cause cross-species infection in a pig model has recently been demonstrated. Rabbit HEV can replicate efficiently in human cell lines. Collectively, these data support the possibility of zoonotic transmission of HEV from rabbits., (Copyright © 2013. Published by Elsevier B.V.)

Hepatitis E is considered as a public health problem in China. To determine the overall molecular epidemiology of hepatitis E virus (HEV) and analyze the situation of cross-species transmission between humans and swine in China over the last 25 years (1986-2011), 626 HEV complete and partial sequences (89 isolates identified by our group) isolated from humans and animals in China were retrieved from GenBank and subjected to phylogenetic analysis. There were three genotypes and 11 sub-genotypes of HEV prevailing in China. Furthermore, rabbit HEVs, of which the genotype is controversial, are also widespread in China. Genotype 1 was the most isolated genotype prior to 2000 and mainly detected in Xinjiang, Beijing and East China. However, genotype 4, which was identified in most regions of China during the last 10 years, has overtaken genotype 1 in frequency of isolation nationwide. Genotype 3 HEV strains have been found only in eastern China and were thought to be imported from Japan. Both genotypes 3 and 4 were found in humans and swine and cross-species transmission from pigs to humans of the two genotypes may have occurred in Northeast, Northwest, North, East and South China. These results indicate that HEV strains with considerable genetic diversity are widespread and the zoonotic transmission between swine and humans appears ubiquitous in China., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV), a causative agent of human hepatitis E, is transmitted through an oral-fecal route, often by contaminated drinking water. Serum specimens were collected from 112 non-A, -B, and -C acute hepatitis patients from 1989 to 2004 in Japan. Of these, 24 patients were found to be positive for anti-HEV IgM and diagnosed with acute Hepatitis E. Seventeen of these patients had a clear history of traveling abroad before disease onset and were counted as cases of imported HEV infection. HEV RNA was detected in 16 of these imported cases, and the nucleotide sequences similar to those of HEV detected in India, Bangladesh, and China were identified. By phylogenetic analysis, the remaining imported case appeared to have been imported from India, even though the patient's travel history was uncertain. These results indicated that some sporadic cases of hepatitis E in Japan are caused by imported HEV, and that phylogenetic analyses enable us to identify the country or area where a patient has been infected., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Rabbit HEV strains were isolated in China from farmed rabbits, which may be a reservoir of a novel genotype of HEV. However, there is little information regarding host range and zoonotic potential of rabbit HEV. A previous study from this group identified 25 specific nucleotide positions as possibly being involved in specifying the host range of HEV and/or in determining the severity of hepatitis E disease, whereas this previous analysis did not extend to the new rabbit HEVs. Consequently the complete genome of the rabbit HEV strain ch-bj-n1 was amplified as overlapping fragments using a combination of reverse-transcription-nested polymerase chain reaction and rapid amplification of cDNA ends. The resulting sequence together with two other rabbit HEVs were compared with 91 other HEV isolates representative of genotypes 1-4. Phylogenetic analysis showed that the novel rabbit HEV strain should be classified into a new HEV genotype which has a closer evolutionary relationship with genotype 3 than genotypes 1, 2 and 4, with 20 of the 25 specific nucleotide positions identified as being present in rabbit HEV genome. Alpha-helix, hydrophilicity, and surface probability plots together with antigenic index analysis of the ORF2 protein were all undertaken to investigate the antigenicity of rabbit HEV. The alpha-helix plot and antigenicity index of the rabbit ORF2 protein was nearly identical to that of genotype 1 HEV isolates from human. Furthermore, 20 possible host range determinants in rabbit HEV were identical to those isolates from zoonotic groups, which may suggest a potential possibility of cross species transmission of rabbit HEV., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hepatitis E was first recognised during an epidemic of hepatitis, which occurred in Kashmir Valley in 1978. The epidemic involved an estimated 52,000 cases of icteric hepatitis with 1700 deaths. The disease had unique clinical and epidemiological features. The epidemic was water-borne with highly compressed epidemic curve. Following the epidemic, secondary waves of hepatitis did not occur. Clinical profile was characterized by cholestasis in around 20% of patients. The disease predominantly occurred in young adults. There was increased incidence and severity of the disease in pregnant women. A subset of patients had distinctive liver histology with bile plugs in the canaliculi and formation of pseudo-ductules by hepatocytes around the bile plugs. All surviving patients had self limiting disease. Sera lacked serological markers of acute hepatitis A and hepatitis B. Based on these data, the possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B hepatitis was postulated. Balayan et al. (1983) successfully transmitted the disease into himself by oral administration of pooled stool extracts of 9 patients from a non-A, non-B hepatitis outbreak which had occurred in a Soviet military camp located in Afghanistan. Reyes et al. (1990) cloned and sequenced hepatitis E virus genome. Over the years, hepatitis E was identified as a major health problem in developing countries with unsafe water supplies and poor sanitary disposal. Data from sero-surveys forced re-evaluation of the epidemiology of hepatitis E and gave an indirect indication to vocationally acquired HEV infections in industrialized countries. Soon, autochthonous hepatitis E was recognised as a clinical problem in such countries. Several animal species especially domestic swine, wild boar and wild deer were found to be reservoirs of hepatitis E virus genotype 3 & 4 in these countries. Human infections occur through intake of uncooked or undercooked meat of the infected animals and pig livers or sausages made from these livers and sold in supermarkets. Chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end stage liver disease was described in organ transplant patients and those with other immunodeficiency states from many European countries. Two recombinant hepatitis E virus vaccines have successfully undergone phase 3 trials., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Molecular characterization of various hepatitis E virus (HEV) strains circulating among humans and animals (particularly swine, deer and boars) in different countries has revealed substantial genetic heterogeneity. The distinctive four-genotype distribution worldwide of mammalian HEV and varying degrees of genetic relatedness among local strains suggest a long and complex evolution of HEV in different geographic regions. The population expansion likely experienced by mammalian HEV in the second half of the 20th century is consistent with an extensive genetic divergence of HEV strains and high prevalence of HEV infections in many parts of the world, including developed countries. The rate and mechanisms of human-to-human transmission and zoonotic transmission to humans vary geographically, thus contributing to the complexity of HEV molecular evolution., (Published by Elsevier B.V.)

Hepatitis E was considered to be endemic infectious disease in developing countries in tropical or subtropical regions with poor sanitary conditions. Large, previously reported outbreaks were mainly due to contaminated water or heavy flooding. Prototype hepatitis E viruses of genotypes I and II were obtained from such endemic cases. In developed countries, in contrast, hepatitis E was rare and diagnosed only in travelers or imported cases. However, the development of accurate diagnostic tests, mainly PCR detection elucidated that autochthonous hepatitis E in developed countries is far more common than previously thought. Although the main route of transmission is food-borne, other routes including blood-borne have been suggested. Recent developments of gene-based diagnostic assays and molecular epidemiology have disclosed the significance of hepatitis E virus infection in developed countries., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A novel hepatitis E virus (HEV) genotype 3 lineage was identified in Slovenian pig herds. Stool samples from six Slovenian pig farms were collected and tested for the presence of HEV RNA. Of 85 individual samples 15 (20.3%) were positive for HEV RNA of which 2/38 (5.3%), 6/21 (28.6%) and 7/26 (26.9%) were from suckling, weanling and fattening pigs, respectively. Additionally, 51 pooled porcine stool samples were tested in one of the biggest pig farm and the estimated infection rate of individual pig was calculated, resulting in 7.8%, 10.6% and 24.2% for suckling, weanling and fattening pigs, respectively. The majority of HEV positive porcine samples were from the same pig farm. Out of 17 Slovenian patients with confirmed recent hepatitis E in the period 1999-2011, the serum samples of 10 patients were tested and 3 samples turned out to be HEV RNA positive. Furthermore, 60 surface water samples were tested throughout the country, of which 2 (3.3%) were positive for HEV RNA, one of them in the near vicinity of a pig farm. All HEV strains were analysed at 5' ORF1 and 5' ORF2 regions and both genome regions confirmed that Slovenian HEV strains represent a distinct genotype 3 lineage, diverse from all other genotype 3 lineages available in GenBank and described in the literature to date. All but one HEV strains detected in pigs in Slovenia represent a monophyletic branch in phylogenetic trees, with a high degree of sequence identity. One human HEV strain belonged to genotype 1 and two to genotype 3 but did not match the new genotype 3 lineage detected in Slovenian pig herds., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hepatitis E is a form of acute hepatitis, which is caused by infection with hepatitis E virus. The infection is transmitted primarily through fecal-oral route and the disease is highly endemic in several developing countries with opportunities for contamination of drinking water. In these areas with high endemicity, it occurs as outbreaks and as sporadic cases of acute hepatitis. The illness often resembles that associated with other hepatotropic viruses and is usually self-limiting; in some cases, the disease progresses to acute liver failure. The infection is particularly severe in pregnant women. Patients with chronic liver disease and superimposed HEV infection can present with severe liver injury, the so-called acute-on-chronic liver failure. In recent years, occasional sporadic cases with locally acquired hepatitis E have been reported from several developed countries in Europe, United States, and Asia. In these areas, in addition to acute hepatitis similar to that seen in highly endemic areas, chronic hepatitis E has been reported among immunosuppressed persons, in particular solid organ transplant recipients. HEV-infected mothers can transmit the infection to foetus, leading to premature birth, increased fetal loss and hypoglycaemia, hypothermia, and anicteric or icteric acute hepatitis in the newborns. Occasional cases with atypical non-hepatic manifestations, such as acute pancreatitis, hematological abnormalities, autoimmune phenomena, and neurological syndromes have been reported from both hyperendemic and non-endemic regions. The pathogenesis of these manifestations remains unclear., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hepatitis E virus (HEV) is an important but extremely understudied pathogen. The mechanisms of HEV replication and pathogenesis are poorly understood, and a vaccine against HEV is not yet available. HEV is classified in the family Hepeviridae consisting of at least four recognized major genotypes. Genotypes 1 and 2 HEV are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 HEV are zoonotic and responsible for sporadic cases worldwide. The identification and characterization of a number of animal strains of HEV from pigs, chickens, rabbits, rats, mongoose, deer, and possibly cattle and sheep have significantly broadened the host range and diversity of HEV. The demonstrated ability of cross-species infection by some animal strains of HEV raises public health concerns for zoonotic HEV infection. Pigs are a recognized reservoir for HEV, and pig handlers are at increased risk of zoonotic HEV infection. Sporadic cases of hepatitis E have been definitively linked to the consumption of raw or undercooked animal meats such as pig livers, sausages, and deer meats. In addition, since large amounts of viruses excreted in feces, animal manure land application and runoffs can contaminate irrigation and drinking water with concomitant contamination of produce or shellfish. HEV RNA of swine origin has been detected in swine manure, sewage water and oysters, and consumption of contaminated shellfish has also been implicated in sporadic cases of hepatitis E. Therefore, the animal strains of HEV pose not only a zoonotic risk but also food and environmental safety concerns., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Hepatitis E virus (HEV) has been identified as an emerging cause of infectious hepatitis over the last years in developed countries. In contrast to travel associated hepatitis E, zoonotic sources of infection are suspected for autochthonous cases in Europe., Objective: Since pigs are known reservoirs of HEV, we tested porcine livers sold as food in Southeastern Germany for the presence of hepatitis E virus RNA., Study Design: We purchased 200 porcine liver samples in 81 butcher shops and grocery stores in Regensburg, Germany. Nucleic acid preparations were tested for the presence of HEV RNA by quantitative real-time PCR (RT-qPCR). HEV isolates from positive samples were characterized by partial sequencing of ORF1 and ORF2 regions in the HEV genome and by phylogenetic analysis., Results: Specimens from eight (4%) of 200 purchased pig livers had detectable HEV RNA amounts. Sequence determination and phylogenetic analysis allowed two novel isolates to be classified as HEV genotype 3, subgenotype 3a (swR437) and 3c (swR269), respectively. Both novel swine HEV isolates showed high sequence homology to isolates obtained from patients with acute HEV infection from the same geographic region., Conclusions: These results support the suggested role of undercooked pig products in food as a source of zoonotic HEV infection for humans. It remains to be clarified if this mechanism of transmission is responsible for the surprisingly high anti-HEV IgG prevalence recently observed in some European countries and the USA., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Hepatitis E virus (HEV) is transmitted via the fecal-oral route and locally acquired sporadic hepatitis E can occur in Western countries. Chronic hepatitis E virus infections have been recently described in solid organ transplant recipients. There is little data on the evolution of hepatitis E in patients immunocompromised for other reasons., Objectives: The aim of this study was to evaluate the clinical course of hepatitis E in patients immunocompromised because of hematological malignancies., Study Design: Starting on November 2003, all patients in the Toulouse University Hospital Hematology Department with unexplained elevated transaminases were tested for hepatitis E using viral RNA detection in serum or stools and serology., Results: Acute hepatitis E was diagnosed in six middle-aged hematology patients. All cases were autochthonous. HEV strains were genotype 3. All patients had a significant increase of transaminases (6-95 upper limit normal) and only two had HEV IgG. Five patients were asymptomatic and one had jaundice. Transmission of HEV occurred between two patients who had overlapping stays in the hematology ward. All five evaluable patients ultimately cleared their HEV but viremia was prolonged over 6 months in three patients and specific treatment had to be postponed in two patients., Conclusion: Screening for HEV should be carried out routinely in hematology patients with elevated transaminases, and patient-to-patient transmission is a concern. Further studies are required to determine whether management of malignancy, particularly stem-cell transplantation should be adapted to HEV status., (Copyright © 2010. Published by Elsevier B.V.)

In 1974, the existence of hepatitis serologically distinct from hepatitis A and B was recognized. They were tentatively designated non-A non-B. They accounted for 90% of post-transfusional hepatitis. During 15 years numerous studies failed to identify agent(s) responsible for these hepatitis. In 1989 the virus responsible for parenteral non-A non-B hepatitis was identified and named hepatitis C virus. Shortly after, the virus responsible for enteral non-A, non-B was also discovered (hepatitis E virus). During these 15 years, a 60% reduction of post-transfusional hepatitis was obtained both by the measures instituted to prevent AIDS transmission and by the introduction of surrogate assays (ALT levels and anti-HBc antibody).

Some cases of hepatitis were non A, non B, non C, non D. Hepatitis E virus (Calicivirus) transmission is fecal-oral similar to that of the hepatitis A virus. Viral hepatitis E is endemic and frequently epidemic in many developing countries, but exceptionally observed in France. A high mortality rate was observed in pregnant women. Recently, ELISA assays for IgM anti-HCV are available. Many hepatitis cases (acute and chronic) are not caused by known viruses (non A-non E). Four Flavivirus like have recently been cloned from infectious tamarin serum, derived from human viral hepatitis. Three viruses GB Virus A (GBV-A), GB Virus B (GBV-B) and GB Virus C (GBV-C) were identified. The GB viruses and HG Virus are not genotypes of hepatitis C Virus (HCV) and perhaps that GBV-A/GBV-C and HGV are closely related. GBV-A could be an indigenous tamarin virus. The new hepatitis (non A-non E) viruses were associated with blood transmission and with chronic diseases. The development of specific diagnostic reagents using polymerase chain reaction (PCR) and ELISA assays are essential to answer many questions on the epidemiology (and the incidence of post-transfusion hepatitis), and the pathogenesis of GBV and HGV viruses.