Hepatitis E Virus: Time to Change the Textbooks

2016 ◽  
Vol 34 (4) ◽  
pp. 308-316 ◽  
Author(s):  
Harry R. Dalton ◽  
Glynn W. Webb ◽  
Ben C. Norton ◽  
Kathy L. Woolson
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Developed Countries ◽  
Genotype 3 ◽  
Primary Host ◽  
Neuralgic Amyotrophy ◽  
Elderly Males ◽  
Wide Range ◽  
Route Of Transmission ◽  
Human Food Chain

Until recently, hepatitis E virus (HEV) was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in such settings. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan), it mainly affects middle-aged/elderly males and it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viremic at the time of donation: Germany 1:1,200, Netherlands 1:2,671, England 1:2,848. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggest that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5 and 10% of the cases, respectively.

scholarly journals Clinical phenotype and outcome of hepatitis E virus–associated neuralgic amyotrophy

Neurology ◽  
2017 ◽  
Vol 89 (9) ◽  
pp. 909-917 ◽  
Author(s):  
Jeroen J.J. van Eijk ◽  
Harry R. Dalton ◽  
Paolo Ripellino ◽  
Richard G. Madden ◽  
Catherine Jones ◽  
...  
Keyword(s):  
Liver Function ◽  
Brachial Plexus ◽  
Hepatitis E Virus ◽  
Clinical Laboratory ◽  
Clinical Phenotype ◽  
Hepatitis E ◽  
Genotype 3 ◽  
Laboratory Findings ◽  
Neuralgic Amyotrophy ◽  
Extensive Damage

Objective:To determine the clinical phenotype and outcome in hepatitis E virus–associated neuralgic amyotrophy (HEV-NA).Methods:Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection.Results:Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12–2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months.Conclusions:Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted.

The entire genome sequence of hepatitis E virus genotype 3 isolated from a patient with neuralgic amyotrophy

2010 ◽  
Vol 42 (5) ◽  
pp. 395-400 ◽  
Author(s):  
Pornpimol Rianthavorn ◽  
Chittima Thongmee ◽  
Noppachart Limpaphayom ◽  
Piyawat Komolmit ◽  
Apiradee Theamboonlers ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Genotype 3 ◽  
Virus Genotype ◽  
Entire Genome ◽  
Neuralgic Amyotrophy ◽  
Entire Genome Sequence

scholarly journals Evaluation of High-Pressure Processing in Inactivation of the Hepatitis E Virus

2019 ◽  
Author(s):  
Neda Nasheri ◽  
Tanushka Doctor ◽  
Angela Chen ◽  
Jennifer Harlow ◽  
Alexander Gill
Keyword(s):  
High Pressure ◽  
Hepatitis E Virus ◽  
Foodborne Pathogen ◽  
Hepatitis E ◽  
Developed Countries ◽  
High Pressure Processing ◽  
Pathogen Inactivation ◽  
Genotype 3 ◽  
Similar Treatment ◽  
Log Reduction

Hepatitis E virus (HEV) causes acute hepatitis with approximately 20 million cases per year globally. While HEV is endemic in certain regions of Asia, Africa and South America, it is considered an emerging foodborne pathogen in developed countries. Based on genetic diversity, HEV is classified into different genotypes, with genotype 3 (HEV-3) being most prevalent in Europe and North America. The transmission of HEV-3 has been shown to be zoonotic and mainly associated with the consumption of raw or undercooked pork products. Herein, we investigated the efficacy of high-pressure processing (HPP) in the inactivation of HEV-3 using a cell culture system. HPP has been indicated as a promising nonthermal pathogen inactivation strategy for treatment of certain high-risk food commodities, without any noticeable changes in their nature. For this purpose, we treated HEV-3 in media as well as in artificially inoculated pork pâté, with different conditions of HPP: 400 MPa for 1 and 5 minutes, as well as 600 MPa for 1 and 5 minutes, at ambient temperature. In general, we observed approximately a 2-log reduction in HEV load by HPP treatments in media; however, similar treatment in the pork pâté resulted in a much lower reduction in viral load. Therefore, the efficacy of HPP treatment in the inactivation of HEV-3 is matrix-dependent.

scholarly journals High prevalence of anti-hepatitis E virus antibodies among blood donors in central Italy, February to March 2014

2016 ◽  
Vol 21 (30) ◽  
Author(s):  
Claudia Lucarelli ◽  
Enea Spada ◽  
Gloria Taliani ◽  
Paola Chionne ◽  
Elisabetta Madonna ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Blood Donors ◽  
Dietary Habits ◽  
Central Italy ◽  
Hepatitis E ◽  
Developed Countries ◽  
Genotype 3 ◽  
Recent Infection ◽  
Assay Sensitivity ◽  
Prevalence Rate Ratio

Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in developed countries, which seems partly due to differences in assay sensitivity. Using validated sensitive assays, we tested 313 blood donors attending a hospital transfusion unit in central Italy in January and February 2014 for anti-HEV IgG and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was the only independent predictor of HEV infection (adjusted prevalence rate ratio = 2.14; 95% confidence interval: 1.23–3.74). Three donors were positive for either anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is therefore hyperendemic among blood donors (80% men 18–64 years-old) from central Italy and associated with local dietary habits. Nearly 1% of donors have acute or recent infection, implying potential transmission to blood recipients. Neither ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV infection.

scholarly journals Detection of Hepatitis E Virus-Specific Immunoglobulin A in Patients Infected with Hepatitis E Virus Genotype 1 or 3

2007 ◽  
Vol 14 (3) ◽  
pp. 276-280 ◽  
Author(s):  
M. Herremans ◽  
E. Duizer ◽  
E. Jusic ◽  
M. P. G. Koopmans
Keyword(s):  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Route Of Transmission

ABSTRACT Currently, diagnosis of acute hepatitis E virus (HEV) in patients is primarily based on anti-HEV immunoglobulin M (IgM) detection. However, several investigations suggest the use of HEV-specific IgA for diagnosing acute HEV infections. We evaluated two commercially available assays, an IgA enzyme-linked immunosorbent assay (ELISA) (Diacheck) and an adapted immunoblot protocol (Mikrogen) for IgA detection and compared the performance in genotype 1- and 3-infected patients. The specificity of the IgA assays was high, with no positive reactions in a control group of 18 acute hepatitis patients who were negative for HEV. The sensitivity calculated in nine PCR-positive type 1-infected patients was 100% in both assays but was clearly lower in genotype 3-infected patients (n = 14), with sensitivities of only 67% and 57% for the ELISA and immunoblot assay, respectively. The lower IgA responses detected in genotype 3-infected patients could be caused by the use of only the genotype 1 and 2 antigens in the serological assays. Interestingly in two patients with possible infection through blood transfusion no response or intermediate IgA responses were detected, and this might confirm the parenteral route of transmission. In both the type 1- and type 3-infected patients both the IgA and IgM responses disappeared simultaneously. We conclude that IgA detection is of limited value for the serodiagnosis of acute HEV cases, particularly with genotype 3.

scholarly journals The Foodborne Transmission of Hepatitis E Virus to Humans

2021 ◽  
Author(s):  
Samantha Treagus ◽  
Conal Wright ◽  
Craig Baker-Austin ◽  
Ben Longdon ◽  
James Lowther
Keyword(s):  
Hepatitis E Virus ◽  
Significant Risk ◽  
Primary Source ◽  
Significant Risk Factor ◽  
Hepatitis E ◽  
Developed Countries ◽  
Broad Host Range ◽  
Genotype 3 ◽  
Zoonotic Pathogen ◽  
Pork Products

AbstractGlobally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.

scholarly journals A Putative Novel Hepatitis E Virus Genotype 3 Subtype Identified in Rabbit, Germany 2016

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1065
Author(s):  
Filip Cierniak ◽  
Felicitas von Arnim ◽  
Gerald Heckel ◽  
Rainer G. Ulrich ◽  
Martin H. Groschup ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Developed Countries ◽  
Viral Disease ◽  
Open Reading Frames ◽  
Nucleotide Exchange ◽  
Genotype 3 ◽  
Virus Genotype ◽  
New Type ◽  
Sequence Characteristics

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.

scholarly journals Light and Darkness: Prevalence of Hepatitis E Virus Infection among the General Population

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
José-Manuel Echevarría
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Developed Countries ◽  
Unknown Etiology ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Urban Sewage ◽  
Technical Issues ◽  
Epidemiology Studies ◽  
The Impact

Human hepatitis E virus (HHEV) spreads early in life among the population in areas endemic for genotype 1 and infects mainly adults in areas endemic for genotype 3, where it would be responsible for about 10% of cases of suspected acute viral hepatitis of unknown etiology and for a number of subclinical, unrecognized infections. The overall prevalence of antibody to HHEV is high in most of the former areas and low in most of the later ones, but wide regional differences have been recorded in both cases. “Hot spots” of HHEV infection would exist for both types of strains in particular regions or among particular populations of the world. Studies on pork derivatives, shellfish bivalves, and vegetables for HHEV contamination at the sale point need to be extended for evaluating the impact of the agent on food safety, and the meaning of the finding of HHEV genotype 1 genomes in urban sewage from developed countries should be established through active surveillance. Consensus about technical issues in regard to anti-HEV testing would improve the knowledge of the HHEV epidemiology. Studies in particular regions and populations, and introduction of molecular diagnosis in the clinical setting as a routine tool, would also be required.

scholarly journals Preliminary study on the detection of hepatitis E virus (HEV) antibodies in pigs and wild boars in Poland

2016 ◽  
Vol 60 (4) ◽  
pp. 385-389 ◽  
Author(s):  
Marcin Weiner ◽  
Małgorzata Tokarska-Rodak ◽  
Dorota Plewik ◽  
Anna Pańczuk ◽  
Adam Szepeluk ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Meat Products ◽  
Hepatitis E ◽  
Developed Countries ◽  
Igg Antibodies ◽  
Genotype 3 ◽  
Pork Production ◽  
Wild Boars ◽  
Preliminary Study ◽  
Positive Results

Abstract Introduction: Although HEV infection in pigs does not pose a major economic risk to pork production, the risk of zoonotic transmission to humans is an important aspect of public health. HEV genotype 3 infections were reported in developed countries in individuals who had consumed raw meat or meat products from deer, wild boars, or pigs. The aim of the study was the analysis of the occurrence of HEV-specific antibodies among wild boars and domestic pigs in Poland. Material and Methods: A total of 290 samples from wild boars and 143 samples from pigs were tested. The antibodies were tested by ELISA. Results: The presence of anti-HEV IgG was demonstrated in 44.1% of pigs and 31.0% of wild boars. Anti-HEV IgG antibodies were detected in 1.4% of samples from pigs and in 2.1% of samples from wild boars at borderline level. The statistical analysis shows significant differences in the positive results for anti-HEV IgG between the groups of pigs and wild boars (P = 0.0263). Conclusion: Regular surveillance of the occurrence of HEV in swine and wild boars should be performed in the future.

scholarly journals Molecular Identification and Characterization of a Genotype 3 Hepatitis E Virus (HEV) Strain Detected in a Wolf Faecal Sample, Italy

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3465
Author(s):  
Vittorio Sarchese ◽  
Paola Fruci ◽  
Andrea Palombieri ◽  
Federica Di Profio ◽  
Serena Robetto ◽  
...  
Keyword(s):  
Faecal Sample ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Developed Countries ◽  
Subtype C ◽  
Genotype 3 ◽  
Red Foxes ◽  
Major Health Problem ◽  
Sequencing Platform ◽  
Porcine Astrovirus

Hepatitis E virus (HEV) infection is a major health problem worldwide. In developed countries, zoonotic transmission of HEV genotypes (Gt) 3 and 4 is caused by the ingestion of raw or undercooked meat of infected pigs and wild boars, the main reservoirs of HEV. However, additional animals may harbour HEV or HEV-related strains, including carnivores. In this study, we investigated the molecular epidemiology of orthohepeviruses in wild canids by screening a total of 136 archival faecal samples, collected from wolves (42) and red foxes (94) in Northwestern Italy. Orthohepevirus RNA was identified in a faecal specimen, collected from a wolf carcass in the province of La Spezia (Liguria Region, Italy). The nearly full-length (7212 nucleotides) genome of the strain HEV/81236/Wolf/2019/ITA (GenBank accession no. MZ463196) was determined by combining a sequence-independent single-primer amplification (SISPA) approach with the Oxford Nanopore Technologies sequencing platform. Upon phylogenetic analysis, the HEV detected in wolf was segregated into clade HEV-3.1, displaying the highest nucleotide (nt) identity (89.0–93.3%) to Gt3 strains belonging to subtype c. Interestingly, the wolf faecal sample also contained porcine astrovirus sequences, endorsing the hypothesis of a dietary origin of the HEV strain due to preying habits.

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