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As a zoonotic pathogen, the hepatitis E virus (HEV) leads to numerous infections in humans with different clinical manifestations. Especially genotype 3, as causative agent of a foodborne zoonosis, is transmitted to humans by ingestion of undercooked or raw meat containing liver from HEV‐infected animals. Although the virus' prevalence and dissemination in hosts like wild boar and pig have been well characterized, HEV is greatly understudied on a molecular level and reliable cell culture models are lacking. For this reason, the present study concentrated on the isolation and subsequent characterization of porcine HEV from tissue samples derived from wild boar and domestic pigs: 222 wild boars hunted in Northern Germany were investigated for the presence of HEV RNA with a detection rate of 5.9%. Three additional HEV‐positive wild boar liver samples as well as an HEV‐positive spleen and a positive kidney from domestic pigs were included. After inoculation of positive samples onto the human hepatoma cell line PLC/PRF/5, cells were grown for several weeks. Successful isolation was confirmed by RT‐qPCR, virus passage, immunofluorescence staining and titration. Overall, 15 strains from a total of 18 RNA‐positive organ samples could be obtained and viral loads >109 RNA copies/ml were measured in cell culture supernatants. Accordingly, 83.3% of the HEV RNA‐positive samples contained infectious hepatitis E viral particles and therefore must be considered as a potential source for human infections. Phylogenetic analyses revealed that all isolated strains belong to genotype 3. Further genetic characterization showed a high degree of sequence variability, but no sequence insertions, in the hypervariable region within the open reading frame 1. [ABSTRACT FROM AUTHOR]

Hepatitis E is a major cause of acute liver disease in humans worldwide. The infection is caused by hepatitis E virus (HEV) which is transmitted in Europe to humans primarily through zoonotic foodborne transmission from domestic pigs, wild boar, rabbits, and deer. HEV belongs to the family Hepeviridae, and possesses a positive-sense, single stranded RNA genome. This agent usually causes an acute self-limited infection in humans, but in people with low immunity, e.g., immunosuppressive therapy or underlying liver diseases, the infection can evolve to chronicity and is able to induce a variety of extrahepatic manifestations. Pig and wild boar have been identified as the primary animal reservoir in Europe, and consumption of raw and undercooked pork is known to pose a potential risk of foodborne HEV infection. In this study, we analysed pig and wild boar liver, faeces, and muscle samples collected in 2019 in Mecklenburg-Western Pomerania, north-east Germany. A total of 393 animals of both species were investigated using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), conventional nested RT-PCR and sequence analysis of amplification products. In 33 animals, HEV RNA was detected in liver and/or faeces. In one individual, viral RNA was detected in muscle tissue. Sequence analysis of a partial open reading frame 1 region demonstrated a broad variety of genotype 3 (HEV-3) subtypes. In conclusion, the study demonstrates a high, but varying prevalence of HEV RNA in swine populations in Mecklenburg-Western Pomerania. The associated risk of foodborne HEV infection needs the establishment of sustainable surveillance and treatment strategies at the interface between humans, animals, and the environment within a One Health framework. [ABSTRACT FROM AUTHOR]

Orthohepevirus C1, also known as rat hepatitis E virus (HEV), has been shown to sporadically cause disease in immunocompromised and immunocompetent adults. While routine serological assays vary in reactivity, rat HEV is not detected in routine HEV RT-PCR. Thus, such infections could be either missed or misclassified as conventional HEV (Orthohepevirus A) infections. We conducted a retrospective screening study among serum and plasma samples from patients suspected of having HEV infection, which were archived at the national consultant laboratory for HAV and HEV between 2000 and 2020. We randomly selected n = 200 samples, which were initially tested reactive (positive or borderline) for HEV-IgM and negative for HEV RNA and re-examined them using a highly sensitive Orthohepevirus C genotype 1-specific in-house RT-qPCR (LoD 95: 6.73 copies per reaction) and a nested RT-PCR broadly reactive for Orthohepevirus A and C. Conventional sanger sequencing was conducted for resulting PCR products. No atypical HEV strains were detected (0 of 200 [0.0%; 95% confidence interval: 0.0%–1.89%], indicating that Orthohepevirus C infections in the investigated population (persons with clinical suspicion of hepatitis E and positive HEV-IgM) are very rare. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a foodborne zoonotic pathogen and known as the causative agent of hepatitis E in humans. The specific role of porcine liver as a vehicle for human HEV infections has been highlighted in different studies. Nevertheless, gaps of knowledge still exist regarding possible HEV cross-contamination both at consumer and production level. Furthermore, people working in the food production industry, e.g. veterinarians and abattoir employees, are exposed to an increased risk of HEV infection. The aim of the present study was to investigate HEV cross-contamination on the surface of porcine liver in a German abattoir. The sample set included 250 samples of porcine liver parenchyma and the corresponding 250 superficial layer samples of the same livers, which were analyzed for the presence of HEV ribonucleic acid (RNA). Afterwards, the initial status of the tested liver parenchyma was compared with the occurrence of HEV RNA in the corresponding superficial layer. HEV RNA was detectable in 34% (85/250) of superficial layer samples, with 58% (49/85) of the samples originated from initially HEV negative livers. To our knowledge, this is the first study that provides an insight in the potential of HEV cross-contamination at abattoir level in Germany. Furthermore, it could be identified that the joint storage of livers in Euro meat containers has a significant impact on the presence of HEV RNA on the surface of porcine liver. [ABSTRACT FROM AUTHOR]

Immunocompromised patients are at risk of chronic hepatitis E which can be acquired by blood transfusions. Currently, screening of blood donors (BDs) for HEV RNA with a limit of detection (LOD) of 2,000 IU/ml is required in Germany. However, this may result in up to 440,000 IU of HEV RNA in blood products depending on their plasma volume. We studied the residual risk of transfusion-transmitted (tt) HEV infection when an LOD of 2,000 IU/ml is applied. Highly sensitive individual donor testing for HEV RNA on the Grifols Procleix Panther system (LOD 7.89 IU/ml) was performed. HEV loads were quantified by real-time PCR. Of 16,236 donors, 31 (0.19%) were HEV RNA positive. Three BDs had viral loads between 710 and 2,000 IU/ml, which pose a significant risk of tt hepatitis E with any type of blood product. Eight BDs had viral loads of >32 to 710 IU/ml, which pose a risk of tt hepatitis E with platelet or plasma transfusions because of their higher plasma volume compared to red blood cell concentrates. Eight of these 11 potentially infectious BDs were seronegative for HEV, indicating a recent infection. Only 8 of 31 donors had viral loads >2,000 IU/ml that would also have been detected by the required screening procedure and 12 had very low HEV loads (<32 IU/ml). Screening of BDs with an LOD of 2,000 IU/ml reduced the risk of tt HEV infection by about 73% for red blood cell concentrates but by just 42% for platelet and fresh frozen plasma transfusions. Single donor screening (LOD <32 IU/ml) should lead to an almost 100% risk reduction. Immunocompromised patients, such as solid organ or hematopoietic stem cell recipients, are at risk of chronic hepatitis E, which can be acquired via blood transfusions. The risk of transfusion-transmitted hepatitis E in these patients may not be sufficiently controlled by (mini-)pool hepatitis E virus RNA screening of blood donors. Single donor screening should be considered to improve the safety of blood products. [Display omitted] • HEV can be transmitted in spite of pool testing of blood donors for HEV RNA. • APCs and FFP are associated with a higher risk of transmitting HEV than RCCs. • Pooled BD testing insufficiently reduces the risk of tt HEV when giving APC and FFP donations. • Single donor testing for HEV RNA should significantly increase the safety of blood products. [ABSTRACT FROM AUTHOR]

BackgroundAwareness of transfusion-transmitted hepatitis E raised in recent years led to the mandatory testing of blood donations in some European countries for hepatitis E virus (HEV) RNA. However, little is known about the epidemiology of HEV infections.AimTo and describe and analyse the epidemiology of HEV infections in blood donors in Germany.MethodsData from routine testing of therapeutic blood products donated between January 2015 and December 2022 at the Uni.Blutspendedienst OWL were analysed at the Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia. A total of 731,630 allogenic blood donations from 119,610 individual blood donors were tested for HEV RNA in minipools of 96 samples. The HEV RNA-positive donations were analysed for the presence of anti-HEV IgM and IgG. The HEV strains were genotyped and various clinical liver-specific parameters were determined.ResultsA total of 497 HEV-positive blood donations were identified, resulting in a yearly incidence of 1:1,474, from which 78.4% of the donations were RNA-only positive. Increased alanine aminotransferase activity was determined in 26.6% of HEV RNA-positive donors and was associated with the detection of IgG antibodies (1.2% anti-HEV IgM-positive, 11.9% anti-HEV IgM- and IgG-positive and 8.5% anti-HEV IgG-positive). An average incidence of 0.084-0.083% HEV RNA-positive donations in June and July in all years was observed, and a higher proportion of HEV RNA-positive men compared with women. All isolated HEV sequences corresponded to genotype 3.ConclusionOur results underline the necessity of HEV RNA screening in blood donations.

The hepatitis E virus (HEV) is one of the most common causes of hepatitis worldwide. HEV is also widespread in many developed countries, where the number of infections is steadily increasing. In those countries, the virus is transmitted mainly through consumption of undercooked or raw food or through contact with animals. Especially, pigs serve as a main reservoir of HEV. Here, we investigated the prevalence of HEV RNA in pork livers and pork meat products to assess the actual risk of HEV infection through food consumption in Germany. A total of 131 pork products were collected from grocery stores and butcher shops between October 2019 and February 2020 and screened for HEV RNA using nested PCR and subsequent sequencing. Overall, 10% of the samples were positive for HEV, including pork livers (5%), spreadable liver sausages (13%) and liver pâté samples (15%). Sequence analyses indicated that the large majority of HEV strains belonged to subtype HEV‐3c, representing the most frequent subtype in Germany. One sample belonged to subtype HEV‐3f. Further sequence analysis revealed large sequence variation between the samples; however, most of the mutations identified were synonymous. Although infectivity of the virus was not tested, the results suggest a considerable risk of HEV infection through food consumption. Therefore, preventive measures should be taken according to a One Health approach. [ABSTRACT FROM AUTHOR]

Background and aims: The incidence of hepatitis E virus (HEV)-infections in industrialized nations has been increasing over the past years. Patients suffering from inflammatory bowel diseases (IBD) may be more prone to transmission. Data on HEV seroprevalence in IBD patients is scarce and has not been reported in German IBD patients. The German Health Examination Survey for Adults 2008–2011, which included 4.422 samples, found a HEV seroprevalence of 16.8%, increasing with age. The aim of the present study was to determine the seroprevalence of anti-HEV IgG in a German cohort of IBD patients, and to explore which parameters have an impact on HEV seroprevalence. Material and methods: This is an uncontrolled, cross-sectional, retrospective monocentric study. Among the patients visiting the IBD outpatient clinic between 25 January, 2019 and 24 September, 2019, 328 patients with Crohn's disease (CD) and 150 patients with ulcerative colitis (UC) were included in the study. IgG antibodies against HEV were determined by enzyme-linked immunosorbent assay. Positive antibody titers were verified using immunoblot analysis. Medical records were reviewed for demographic and clinical parameters to identify potential risk factors for HEV infection. Results: The prevalence of anti-HEV IgG antibodies was 17.4% in CD patients and 24.7% in UC patients. No patient with positive HEV PCR was detected. Greater age of CD und UC patients and longer duration of anti-interleukin 12/23 treatment in CD patients were associated with higher anti-HEV IgG antibody rates. Conclusions: In summary, we conclude that patients with UC have a higher anti-HEV IgG antibody prevalence than the general population in Germany, and that immunosuppressive therapy may carry no higher risk for HEV infection. [ABSTRACT FROM AUTHOR]

A steep rise in Hepatitis E diagnoses is currently being observed in Germany and other European countries. The objective of this study was (i) to assess whether this trend mirrors an increase in infection pressure or is caused by increased attention and testing and (ii) estimate individual and population-based Hepatitis E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured anti-HEV IgG prevalence in 10 407 adults participating in two linked, population-representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this period, we found a moderate but statistically significant decline of overall anti-HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence increased with age and peaked in persons born between 1935 and 1959 suggesting a past period of increased infection pressure. Paired samples of individuals participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and seroreversion rates of 6.2% and 22.6% among seronegative and seropositive individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions per year in the German population. While anti-HEV seroprevalence has decreased in the last decade, infection pressure and seroincidence remains high in Germany. Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to an increased awareness of clinicians and indicate that still there is a gap between incident and diagnosed cases. Studies on the true burden of the disease, specific risk factors and sources of autochthonous infections as well as targeted prevention measures are urgently needed. [ABSTRACT FROM AUTHOR]

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Rabbit-associated hepatitis E viruses (HEVs) cause zoonotic infections. We investigated 2,389 hares in Germany during 2007-2014. Complete genome characterization of a hare-associated HEV strain revealed close genomic relatedness to rabbit-associated HEV strains. Although hare-specific HEV seroprevalence was low, at 2.6%, hares represent a potential source of sporadic HEV infections. [ABSTRACT FROM AUTHOR]

Background: In Germany, 17% of the general human population have antibodies to hepatitis E virus (HEV) (recomLine HEV-IgG/IgM immunoassay [Mikrogen GmbH]). Wild boars represent an animal reservoir for HEV genotype 3, which is the common genotype in Germany. We estimated the seroprevalence among hunters with contact to wild boars to identify factors that may be associated with past or present HEV infection.Methods: In 2013, the local veterinarian authority in a district in Central Germany attended meetings of hunters who provided blood specimens and completed a questionnaire collecting information on age, sex, hunting-related activities and consumption of wild boar meat. Specimens of wild boars were taken during drive hunts in this district during the season 2012/2013. All specimens were tested for HEV RNA and anti-HEV IgM and IgG antibodies. Log-binomial regression was used to estimate prevalence ratios (PR) for the hunters.Results: Of 126 hunters (median age 55; 94% male) 21% tested positive for anti-HEV IgG antibodies (95% confidence interval [CI] 13-28%) (recomWell HEV IgG assay [Mikrogen GmbH]). Anti-HEV prevalence was highest in the age group of the 70-79-year-olds (67%; 95% CI 39-95%). Wild boars showed an average anti-HEV prevalence of 41%. HEV RNA was detected in 4/22 (18%) liver specimens and in 1/22 (4.5%) muscle specimens. Most wild boars were tested positive for HEV RNA (3/10; 30%) and HEV-specific antibodies (7/15; 47%) in the southwestern part of the district. Hunters preferring this hunting ground had a lower anti-HEV prevalence when gloves were frequently used during disembowelling of wild boars compared to hunters using gloves never or infrequently (age-adjusted PR 0.12; 95% CI 0.02-0.86).Conclusions: Hunters may benefit from wearing gloves when in contact with blood or body fluids of HEV animal reservoirs. Anti-HEV prevalence among the hunters of this study did not significantly differ from that of the general population suggesting that other factors play a major role in the epidemiology of HEV in Germany. [ABSTRACT FROM AUTHOR]

Background Hepatitis E virus ( HEV) is transmissible by transfusion. More data are needed about seroprevalence, incidence, and viremia in blood donors for the assessment of risk of transfusion-transmitted ( TT)- HEV infections. Study Design and Methods Samples from 1019 whole blood donors were tested for anti- HEV immunoglobulin ( Ig) G by enzyme-linked immunosorbent assay and Western blot. The incidence of HEV and presence of HEV RNA in donors who seroconverted were determined by testing archive samples and recipients of viremic donations were traced. Anti- HEV IgM and alanine transaminase ( ALT) testing were also performed to assess the value of such measures in the prevention of TT-HEV infections. Results A total of 69 of 1019 donors tested positive for anti- HEV IgG (6.8% seroprevalence), and seroconversion for anti- HEV IgG occurred in seven of 69 donors within 2 years (incidence, 0.35%/year). Three of seven (42.8%) seroconverting donors provided an archive sample in which HEV RNA was detectable. One recipient of these donations was traceable; anti- HEV IgG, IgM, and HEV RNA testing were negative 41 days after transfusion. Neither ALT levels nor anti- HEV IgM detection correlated with the presence of HEV RNA. Conclusions The seroprevalence of HEV was 6.8%, and the annual incidence 0.35%. HEV RNA was detectable in several seroconverting donors, without evidence for HEV transmission in the only traceable recipient. Since neither ALT nor anti- HEV IgM testing correlate with the presence of HEV RNA, HEV nucleic acid testing currently provides the only method for the prevention of TT-HEV infection. However, before implementation, more data about clinical relevance of TT-HEV infections and infectious dose of HEV are required. [ABSTRACT FROM AUTHOR]

An increasing number of acute autochthonous human hepatitis E virus (HEV)-infections was noticed in Germany and other developed countries, most likely the result of a zoonotic virus transmission from pig, wild boar and deer. Currently there is still a lack of profound data concerning the actual prevalence of HEV-specific antibodies in domestic pig herds in Germany, in particular for regions with high pig density, and its age-dependency. 2273 domestic pig sera were collected in 2011 mainly from Bavaria, North Rhine-Westphalia and Lower Saxony from areas having a high pig density. Initially, 420 randomly selected pig sera were tested in three commercially available and in two in-house HEV-antibody ELISAs. 43.6% (183/420) to 65.5% (275/420) of the sera were demonstrated to be reactive against human pathogenic HEV genotypes 1 and/or 3. The majority of sera reacted only weakly or not at all with the rat HEV antigen with very few sera showing a stronger reactivity to this antigen compared to the genotype 3 antigen. The results of all three HEV-IgG tests, i.e. the PrioCHECK® HEV Ab porcine ELISA kit, the ID Screen® Hepatitis E Indirect Multi-species ELISA kit and the genotype 3 in-house ELISA were in good accordance. Therefore, the remaining sera were tested using the PrioCHECK® HEV Ab porcine ELISA kit. Samples with a borderline result were finally determined by application of the conjugate-modified recomLine HEV IgG assay. A total of 1065 of the 2273 sera (46.9%) were found to be anti-HEV IgG-positive. While 38.4% (306/796) of fatteners (age between 3 and 9 months) exhibited HEV-specific antibodies, 51.4% (759/1477) of sows (age older than 9 months) exhibited anti-HEV antibodies (P <0.001). Fatteners kept in Southern Germany had a significantly higher HEV IgG prevalence compared to fatteners kept in the high pig density federal states North Rhine-Westphalia and Lower Saxony but also in German federal states with a low pig density. In conclusion, the present study clearly demonstrates that a high percentage of domestic pigs in Germany have had contact with HEV. Seroprevalence depends on the pig's age and herd origin with the most significant regional variations for fatteners. The presence of anti-HEV-free herds may indicate that it is feasible to establish and sustain HEV-free pig herds. HEV seroprevalence still depends on the assay used for testing. This demonstrates an urgent need for test validation. [ABSTRACT FROM AUTHOR]

An acute infection with hepatitis E virus (HEV) genotype 3 subtype c was diagnosed in a patient with chronic lymphatic B-cell leukemia 6 weeks after the infusion of donor lymphocytes. Despite intensive care the patient died 39 days after admission due to pericardial effusion that was related to acute liver failure. We suggest that diagnostic procedures for detection of HEV infection should be seriously considered for the immunocompromised patient with elevated liver enzymes in the absence of a travel history to HEV endemic countries. [ABSTRACT FROM AUTHOR]

Abstract: Zoonotic hepatitis E virus (HEV) infection in industrialised countries is thought to be caused by transmission from wild boar, domestic pig and deer as reservoir hosts. The detection of HEV-specific antibodies in rats and other rodents has suggested that these animals may represent an additional source for HEV transmission to human. Recently, a novel HEV (ratHEV) was detected in Norway rats from Hamburg, Germany, showing the typical genome organisation but a high nucleotide and amino acid sequence divergence to other mammalian and to avian HEV strains. Here we describe the multiple detection of ratHEV RNA and HEV-specific antibodies in Norway rats from additional cities in north-east and south-west Germany. The complete genome analysis of two novel strains from Berlin and Stuttgart confirmed the association of ratHEV to Norway rats. The present data indicated a continuing existence of this virus in the rat populations from Berlin and Hamburg. The phylogenetic analysis of a short segment of the open reading frame 1 confirmed a geographical clustering of the corresponding sequences. Serological investigations using recombinant ratHEV and genotype 3 capsid protein derivatives demonstrated antigenic differences which might be caused by the high amino acid sequence divergence in the immunodominant region. The high amount of animals showing exclusively ratHEV RNA or anti-ratHEV antibodies suggested a non-persistent infection in the Norway rat. Future studies have to prove the transmission routes of the virus in rat populations and its zoonotic potential. The recombinant ratHEV antigen generated here will allow future seroepidemiological studies to differentiate ratHEV and genotype 3 infections in humans and animals. [Copyright &y& Elsevier]

Due to the increasing number of non-travel-associated hepatitis E virus (HEV) infections observed in several industrialised countries including Germany, there is a substantial interest in the characterisation of risk factors and transmission routes relevant to autochthonous HEV infections. Autochthonous cases are believed to be the result of a zoonotic HEV transmission from pigs, wild boars and deer. Recently, a high prevalence of HEV-specific antibodies in the German domestic pig population has been demonstrated. Thus, one may assume a higher prevalence of HEV-specific antibodies in humans with occupational exposure to pigs. In this study, sera obtained from 24 slaughterers, 14 meat inspectors, 46 pig farmers and 22 veterinarians were tested for the presence of HEV-specific antibodies using a line immunoassay. For comparison, sera obtained from 116 age- and gender-matched blood donors were also included. Twenty eight per cent (28.3%; 30/106) of the swine-exposed humans and 15.5% (18/116) of the blood donors without contact to pigs exhibited IgG-antibodies determined as reactive (i.e. borderline or positive) against HEV. Thus, an increased risk of HEV infection in humans occupationally exposed to pigs and particularly for slaughterers (41.7%; 10/24) was demonstrated. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is largely confined to travelers returning from endemic areas, but the number of autochthonous cases of acute HEV infections in developed countries is increasing. Reservoirs for HEV are surface water, wild boar meat, and raw or undercooked pork meat. Usually, hepatitis E is a self-limiting disease presenting with acute hepatitis as a major clinical symptom. The seroprevalence of anti-HEV-IgG was investigated in 833 serum samples routinely collected from patients admitted to the university hospital in Frankfurt a. M., Germany (FFM) between 01.06.2008 and 31.12.2010. After determination of overall seroprevalence, we tested serum samples from patients diagnosed with acute elevation of liver enzymes (AELE), psychiatric (PSYCH), infectiological patients and serum samples from the red-cross blood donor service in FFM for anti-HEV-IgG using an ELISA. Between 01.06.2008 and 31.12.2010, 833 serum samples were analyzed for anti-HEV-IgG using an ELISA. We observed an overall seroprevalence of anti-HEV-IgG of 11.2% (95%CI: 9.6-13.2). Significantly higher rate of seropositivity was found in the group of PSYCH (26.0%; 95%CI: 14.63-40.34) and AELE (30.0%; 95%CI: 17.86-44.61). Overall seroprevalence of anti-HEV-IgG in FFM is higher than in Germany on average. The group of AELE and PSYCH shows significantly more often marker of HEV infections than other groups in our collective. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the causative agent of an acute self-limiting hepatitis in humans. In industrialized countries, autochthonous cases are linked to zoonotic transmission from domestic pigs, wild boar and red deer. The main route of human infection presumably is consumption of contaminated meat. Farmers, slaughterers and veterinarians are expected to be risk groups as they work close to potentially infected animals. In this study, we tested four Escherichia coli-expressed segments of the capsid protein (CP) of a German wild boar-derived HEV genotype 3 strain for their diagnostic value in an indirect immunoglobulin G (IgG) ELISA. In an initial validation experiment, a carboxy-terminal CP segment spanning amino acid (aa) residues 326-608 outperformed the other segments harbouring aa residues 112-608, 326-660 and 112-335. Based on this segment, an indirect ELISA for detection of anti-HEV IgG antibodies in human sera was established and validated using a commercial line immunoassay as reference assay. A total of 563 sera from forestry workers of all forestry offices of Brandenburg, eastern Germany and 301 sera of blood donors from eastern Germany were surveyed using these assays. The commercial test revealed seroprevalence rates of 11% for blood donors and 18% for forestry workers. These rates are in line with data obtained by the in-house test (12 and 21%). Hence, the in-house test performed strikingly similar to the commercial test (sensitivity 0.9318, specificity 0.9542). An initial screening of forestry worker and blood donor sera with a corresponding CP segment of the recently discovered Norway rat-associated HEV revealed several strong positive sera exclusively in the forestry worker panel. Future investigations have to prove the performance of this novel IgG ELISA in large-scale seroepidemiological studies. In addition, the observed elevated seroprevalence in a forestry worker group has to be confirmed by studies on groups of forestry workers from other regions. The epidemiological role of ratHEV in human disease should be assessed in a large-scale study of risk and non-risk groups. [ABSTRACT FROM AUTHOR]

Human hepatitis E virus infections may be caused by zoonotic transmission of virus genotypes 3 and 4. To determine whether rodents are a reservoir, we analyzed the complete nucleotide sequence of a hepatitis E-like virus from 2 Norway rats in Germany. The sequence suggests a separate 9enotype for this hepatotropic virus. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis E virus is the causative agent of an acute hepatitis in humans. In industrialized countries, autochthonous hepatitis E cases in the past were mainly of undetermined origin, whereupon nowadays some cases may be linked to zoonotic transmission of HEV from pigs and wild boars. In contrast to several European countries the HEV status of German domestic pigs and a possible risk of transmission are unknown so far. Here, a novel peptide-based ELISA was used to detect HEV-specific antibodies in 1072 sera from German domestic pigs resulting in an average seroprevalence of 49.8% indicating widespread HEV infections in these animals. A comparative testing of 321 randomly selected sera revealed a seroprevalence of 64.8% when using a commercially available ELISA and 43.9% for the novel peptide-based ELISA but concordant results were obtained in both tests only for 56.1% of the sera. Additional re-testing of 23 randomly selected sera with a modified commercially available immunoblot revealed discordant results also. The use of different antigens and the measurement of different immunoglobulin classes are considered to be responsible for the observed variations of the results. Though the present study revealed a high seroprevalence of HEV in the German domestic pig population and a potential risk of transmission to humans, the differing results of the tests highlight the necessity of a standardization of serological assays for comparative seroprevalence and longitudinal studies. [Copyright &y& Elsevier]

Abstract: Hepatitis E infection is usually a self-limiting disease and an important cause of acute hepatitis in tropical and subtropical regions where the virus is endemic. In industrialized countries, sporadic cases of acute hepatitis E virus (HEV) infections have been described and the number of documented autochthonous infections seems to be increasing. We report three sporadic cases of autochthonous hepatitis E infections in Southwestern Germany which presented at our university hospital within two years. All cases were men who presented with acute hepatitis, icterus and elevated liver. In case 1 and case 2, liver biopsy revealed acute hepatitis, both patients were positive for anti-HEV antibodies, case 1 was also positive for HEV RNA with a viral load of 3.0×103 copies/ml in serum. In case 3, anti-HEV antibodies were detectable and HEV RNA was detected in serum (4.3×103 copies/ml) and stool (1.4×106 copies/ml). None of the patients had a recent travel history outside Germany and close contact to animals has been denied. HEV sequence analysis of two patients revealed genotype 3 with homologies to other European isolates and isolates from swine. Thus the source of infection remains unclear. Hepatitis E should be considered in differential diagnosis in patients with unexplained hepatitis and patients with acute hepatitis, whatever their age or travel history might be, should be tested for HEV. [Copyright &y& Elsevier]

Background Although Europe is supposed to be non-endemic for hepatitis E virus (HEV), locally acquired human cases are registered, and a relatively high prevalence for anti-HEV was found in blood donors in some European countries. Transfusion–transmitted infections by contaminated blood products were reported in Japan and sporadically in Europe. Materials and Methods Several samples from a plasma donor were screened with a highly sensitive quantitative HEV real-time polymerase chain reaction and the full-length genome was generated. Serology was performed with two different commercially available ELISA kits. Results The full-length genome sequence of human HEV was identified using samples from a plasma donor with acute self-limiting hepatitis. Plasma donated 2 weeks before onset of elevated liver enzyme levels was already positive for HEV RNA (104 copies/ml). High viraemia (106 copies/ml) correlated with the detection of anti-HEV IgM in the first blood sample with increased alanine transaminase levels. Phylogenetic analyses grouped the isolate within genotype 3, subtype 3f. Conclusion The sequence analyses and the epidemiological data revealed that the plasma donor was most probably infected with a swine HEV. This case supports the ongoing discussion of an obligatory HEV nucleic acid testing of blood products for special recipient risk groups. [ABSTRACT FROM AUTHOR]

Background: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. Methods: A cohort study of 82 pregnant women with a history of migration and corresponding delivery of newborns in Germany was conducted. Results: Overall, 9% of sera tested positive for anti-HEV IgG. None of the patients tested positive for anti-HEV IgM, schistosomiasis, or echinococcus serology. Birth weights were below the 10th percentile for gestational age in 8.5% of the neonates. No association between HEV serology and fetal growth restriction (FGR) frequency was found. Conclusions: In comparison to German baseline data, no increased risk for HEV exposure or serological signs of exposure against schistosomiasis or echinococcosis could be observed in pregnant migrants. An influence of the anti-HEV serology status on fetal growth restriction could not be found. [ABSTRACT FROM AUTHOR]

Viral hepatitis A to E describes various infectious inflammations of the liver parenchyma that are caused by the hepatitis viruses A to E (HAV, HBV, HCV, HDV, and HEV). Although the clinical pictures are similar, the pathogens belong to different virus families and differ in terms of pathogenesis, transmission routes, clinical course, prevention, and therapy options. In Germany, there is mandatory reporting according to the Infection Protection Act (IfSG) for direct or indirect laboratory evidence and for suspicion, illness, and death of viral hepatitis. The data are transmitted to the Robert Koch Institute.In this article, on the basis of published studies and notification data, we describe the epidemiology of hepatitis A to E as well as current challenges and prevention approaches. In particular, the latter contains the improvement of existing vaccination recommendations (hepatitis A and B); improvement of access to prevention, testing, and care including therapy with antiviral drugs (hepatitis B, C, and D) and the detection and prevention of foodborne infections and outbreaks; and improvements in the field of food safety (hepatitis A and E)., (© 2022. The Author(s).)

The hepatitis E virus (HEV) is an etiological agent of acute hepatitis in humans. In addition, chronic infections resulting in fatal liver cirrhosis currently emerge in immunosuppressed transplant patients. The number of notified hepatitis E cases in Germany has steeply increased in recent years. Here, genotype 3, which can be zoonotically transmitted from animals to humans, is predominant. The main reservoirs are pigs and wild boars, which show no signs of infection. In this article, the distribution of HEV in animals in Germany, possible transmission pathways, and especially the importance of food as a transmission vehicle are presented based on the current scientific literature.HEV is widely spread among domestic pigs and wild boars in Germany and the virus is mainly transmitted by direct contact or by consumption of food produced from those animals. However, if HEV RNA is detected in specific food it is often unclear whether the contained virus is still infectious or inactivated by the conditions during production. Recent studies indicate a high stability of HEV against different physicochemical conditions, whereas - among others - the virus can be efficiently inactivated by heating. Therefore, proper heating of pork meat and liver prior to consumption in general is recommended. For risk groups, avoiding shortly cured raw sausages is an additional suggestion.Further research is necessary to identify relevant risk food products, to investigate alternative transmission pathways, and to develop efficient measures in order to reduce or prevent zoonotic transmissions of the virus in future., (© 2021. The Author(s).)

Hepatitis E is an emerging viral disease that is the leading cause of viral hepatitis in the world. The vast majority of hepatitis E cases in developed countries are caused by zoonotic genotypes 3 and 4 of hepatitis E virus (HEV) for which pig and wild boar and to lesser extent rabbits are the main reservoir. According to recent reports rabbits are a source of human HEV infection and highlight the risk of zoonotic foodborne transmission. Here we report the molecular analysis of a novel HEV strain identified in a rabbit during a countrywide surveillance of rabbits and hares in Germany, 2016. The analysis of the complete genome reveals characteristics of a putative novel recombinant subtype of the species Orthohepevirus A within the clade of genotype 3 but not closely related to any known subtypes. Importantly, the genome of this strain possesses a nucleotide exchange in the overlapping region of open reading frames ORF2/ORF3 interfering with a broadly applied diagnostic real-time RT-PCR. In conclusion, a new type of HEV strain was identified in a German rabbit with atypical and novel sequence characteristics. [ABSTRACT FROM AUTHOR]

In the last decade, the number of reported hepatitis E virus (HEV) infections in Germany, including Bavaria, has continued to rise. In order to identify risk factors associated with HEV infection, we investigated notified hepatitis E cases from Bavaria during 2017. The project "Intensified Hepatitis E Surveillance in Bavaria" included interviews with questionnaires, collection and genotyping of stool, serum and food samples. In addition, certain risk factors were examined in a sample comparison with healthy population using univariable analysis and logistic regression. In total, 135 hepatitis E cases from Bavaria were included in the analysis. Mean age for women was 46 (range 20-74) years and 47.5 (range 20-85) for men. 56 of the cases (41.5%) were asymptomatic. Among the symptomatic cases, both men and women were equally affected with symptoms like fever (16.3%), jaundice (18.8%) and upper abdominal pain (28.2%). 145 human samples (serum, stool) and 6 food samples were collected. 15.9% of the human samples (n = 23) were positive for HEV RNA by reverse-transcription quantitative real-time PCR (RT-qPCR). Identified risk factors significantly associated with hepatitis E were sausage consumption with odds ratio 9.6 (CI 1.3-70.1), fish with OR 2.2 (CI 1.1-4.4) and cat ownership with OR 1.9 (CI 1.3-3.0) in multivariable analyses. Further investigation is needed to confirm the role of fish in HEV transmission. Autochthonous HEV genotype 3 is prevalent in Bavaria and there could be more transmission routes contributing to the spread of HEV than previously known. Undercooked meat, offal, sausages, fish, shellfish and contact with animals and pets are possible sources for infection., (© 2021. The Author(s).)

Hepatitis E virus (HEV) is a common cause of acute hepatitis in endemic areas. Yet reports on autochthonous cases in other areas such as middle Europe are increasing. Here we report on a patient, who obviously acquired his HEV infection in Germany. Sequence analysis of the virus gained from his serum revealed homologies to other European isolates and swine isolates. [ABSTRACT FROM AUTHOR]

In the last few years it has been realized that the hepatitis E virus (HEV) is endemic in most industrialized countries and that it is a zoonotic disease. Potential reservoirs for HEV have been identified to be wild boars and deers, but HEV has also been found in domestic pigs and other animals. Due to the probable spread of the virus via contaminated food or contact to infected animals, HEV antibodies are present in more than 16% of the German adult population and rates are increasing with age. We collected blood from 104 wild boars in southern Germany and the border region of Alsace. We found an anti-HEV seroprevalence of 11.5% in our cohort, using ELISA. Furthermore, we observed active infection in 3.85% of the animals by positive HEV PCR in the sera of the boars. In our cohort, no regional differences of seroprevalence or active infection were seen. Sequencing revealed rather close homology of some detected HEV sequences to genotypes isolated from patients in Germany. Hence wild boars are a potential source of HEV infection in Middle Europe and the rate of infectious animals is quite high.

BackgroundNotified cases of hepatitis E have increased 40-fold in the past 10 years in Germany. Food safety is a major concern as hepatitis E virus (HEV) RNA has been detected in ready-to-eat retail-level food products. The objective of this case-control study was to assess risk factors for autochthonous symptomatic hepatitis E and explore reasons for delays in diagnosis. Methods: Demographic, clinical and exposure data from notified hepatitis E cases and individually matched population controls were collected in semi-standardised telephone interviews. Conditional logistic regression analysis was used to calculate matched odds ratios (mOR) and population attributable fractions (PAF). Results: In total, 270 cases and 1,159 controls were included (mean age 53 years, 61% men in both groups). Associated with disease were: consumption of undercooked pork liver, pork, wild boar meat, frankfurters, liver sausage and raw vegetables; contact with waste water (occupational) and various host factors (mORs between 1.9 and 34.1, p value < 0.03). PAF for frankfurters and liver sausage were 17.6%, and 23.6%, respectively. There were statistically significant differences in the clinical presentation and hospitalisation proportion of acute hepatitis E in men and women. Diagnosis was preceded by more invasive procedures in 29.2% of patients, suggesting that hepatitis E was not immediately considered as a common differential diagnosis. Conclusions: Our study suggests that there are indeed sex-specific differences in disease development and lends important epidemiological evidence to specific ready-to-eat pork products as a major source for autochthonous hepatitis E. A review of existing consumer recommendations and production methods may be indicated.

Abstract: Hepatitis E virus (HEV) is well-known to cause endemic outbreaks of hepatitis in tropical countries, mostly caused by HEV genotypes 1 or 2 and transmitted from humans to humans via the fecal–oral route. In contrast, HEV genotypes 3 or 4 are commonly encountered as sporadic cases in a non-endemic setting; these autochthonous cases are transmitted from animals to humans and commonly affect elderly male subjects. We report a five-month-old caucasian girl presenting with diarrhea, emesis, and elevated ALT. Surprisingly, acute infection with Hepatitis E virus (HEV) genotype 3 was laboratory-confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing. Thirteen months later, RT-PCR for HEV from stool tested negative whereas anti-HEV IgG in serum tested positive. Neither HEV RNA nor anti-HEV antibodies could be detected in stool or serum of the parents. To our knowledge, this is the first pediatric case of a HEV infection in Germany. Thus, HEV should be included into the differential diagnosis of pediatric infectious liver and bowel disease. [ABSTRACT FROM AUTHOR]

Background & Aims: In Western countries, infection with the hepatitis E virus (HEV) is considered to be rare and imported from endemic regions. However, the prevalence of HEV infection has increased among adults in central Europe. HEV infection can cause acute liver failure (ALF), but there have been only a few confirmed cases of HEV-associated ALF in Europe. We investigated the number of cases of indeterminate ALF associated with HEV infection., Methods: We performed a retrospective analysis of 80 patients diagnosed with ALF or acute hepatitis at the University Hospital Essen in Germany from November 2006 through December 2013. Clinical data were collected from the hospital databases; archived sera were tested for IgG and IgM against HEV, as well as HEV RNA., Results: Sera from 12 patients (15%) tested positive for IgG against HEV IgG; 7 of these samples did not test positive for HEV IgM or HEV RNA. Sera from 64 patients (80%) did not test positive for IgG or IgM against HEV or HEV RNA. Sera from 8 patients (10%) tested positive for HEV RNA (only 4 of these were positive for HEV IgG) and had clinical findings to support acute HEV infection., Conclusions: In a hospital in Germany, approximately 10% to 15% of patients with ALF had evidence for HEV infection. Serologic tests for IgG against HEV are insufficient to identify or exclude HEV infection; tests for HEV RNA also should be performed on patients with ALF of ambiguous etiology., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The article presents a study which examines the role of hepatitis E virus (HEV) on the elevating levels of alanine transminase (ALT) among German blood donors. The study notes that the positive samples of the donors of the ALT negates the assumed presence of HEV RNA. Moreover, it notes that the case reported by Adlhoch et. al only demonstrated a diagnostic window period of HEV, hence, further studies are required to come up with efficient findings.