{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T05:07:37Z","timestamp":1764997657945,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis E virus (HEV) is a global health problem, causing an estimated 20 million infections annually. Thus, the management of HEV requires special consideration. In developed countries, hepatitis E is mainly recognized as a foodborne disease (mainly transmitted via undercooked meat consumption) that is generally caused by genotype 3 and 4 circulating in various animals, including pigs and wild boars. The current absence of officially recognized protocols for the analysis of HEV in foods and the lack of awareness of this disease among healthcare workers, together with the high percentage of asymptomatic cases, make HEV infection highly underestimated. Most HEV-3 infections in immunocompetent individuals are self-limited. Nevertheless, the possibility of serious forms of liver disease, especially in patients with co-morbidities, should be considered because it can lead to a fatal outcome. Here, we report a case of fatal hepatitis related to HEV-3 infection in a 67-year-old male patient with underlying chronic liver disease (CLD) and living in a region where a high prevalence and genetic heterogeneity of HEV-3 in wild boar has been recently demonstrated. Our case report describes the interdisciplinary approach used (from the diagnosis to the virus phylogenetic characterization) in order to improve epidemiologic HEV surveillance in central Italy.<\/jats:p>","DOI":"10.3390\/v16121869","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T06:58:58Z","timestamp":1733122738000},"page":"1869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Case of Fatal Hepatitis Related to HEV-3 Infection in Central Italy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6337-5999","authenticated-orcid":false,"given":"Monica","family":"Borghi","sequence":"first","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale dell\u2019Umbria e delle Marche, 06126 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-3425","authenticated-orcid":false,"given":"Alessandro","family":"Graziani","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Marini","sequence":"additional","affiliation":[{"name":"Microbiology Unit, Santa Maria della Misericordia Hospital, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Madonna","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Unit of Viral Hepatitis and Oncovirus and Retrovirus Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-041X","authenticated-orcid":false,"given":"Umbertina","family":"Villano","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Unit of Viral Hepatitis and Oncovirus and Retrovirus Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-0539","authenticated-orcid":false,"given":"Elisabetta","family":"Suffredini","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-8476","authenticated-orcid":false,"given":"Teresa","family":"Vicenza","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elida","family":"Mataj","sequence":"additional","affiliation":[{"name":"Institute of Public Health (ISHP), 1000 Tirana, Albania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-5510","authenticated-orcid":false,"given":"Roberto","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Unit of Viral Hepatitis and Oncovirus and Retrovirus Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Rita","family":"Ciccaglione","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Unit of Viral Hepatitis and Oncovirus and Retrovirus Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-0127","authenticated-orcid":false,"given":"Barbara","family":"Camilloni","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"},{"name":"Microbiology Unit, Santa Maria della Misericordia Hospital, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Bozza","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"},{"name":"Microbiology Unit, Santa Maria della Misericordia Hospital, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","first-page":"e38101","article-title":"Fulminant Hepatitis A and E Co-Infection Leading to Acute Liver Failure: A Case Report","volume":"15","author":"Malik","year":"2023","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.3748\/wjg.v26.i37.5543","article-title":"Hepatitis E Virus: Epidemiology, Diagnosis, Clinical Manifestations, and Treatment","volume":"26","author":"Aslan","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a031724","DOI":"10.1101\/cshperspect.a031724","article-title":"Hepatitis E Virus Genome Structure and Replication Strategy","volume":"9","author":"Kenney","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","first-page":"4886","article-title":"Public Health Risks Associated with Hepatitis E Virus (HEV) as a Food-borne Pathogen","volume":"15","author":"Ricci","year":"2017","journal-title":"EFSA J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.sjbs.2021.09.003","article-title":"Bin Hepatitis E Virus: An Emerging Enigmatic and Underestimated Pathogen","volume":"29","author":"Raji","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"De Sabato, L., Di Bartolo, I., Lapa, D., Capobianchi, M.R., and Garbuglia, A.R. (2020). Molecular Characterization of HEV Genotype 3 in Italy at Human\/Animal Interface. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00137"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yadav, K.K., and Kenney, S.P. (2021). Hepatitis E Virus Immunopathogenesis. Pathogens, 10.","DOI":"10.3390\/pathogens10091180"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejogrb.2020.11.052","article-title":"Viral Hepatitis in Pregnancy","volume":"256","author":"Chilaka","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0140-6736(10)61030-6","article-title":"Efficacy and Safety of a Recombinant Hepatitis E Vaccine in Healthy Adults: A Large-Scale, Randomised, Double-Blind Placebo-Controlled, Phase 3 Trial","volume":"376","author":"Zhu","year":"2010","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jhep.2006.09.016","article-title":"Hepatitis E Virus (HEV) Infection in Patients with Cirrhosis Is Associated with Rapid Decompensation and Death","volume":"46","author":"Singh","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1053\/jhep.2002.34856","article-title":"Hepatitis E Virus Superinfection in Patients with Chronic Liver Disease","volume":"36","author":"Hamid","year":"2002","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2893.2007.00858.x","article-title":"Fulminant Liver Failure from Acute Autochthonous Hepatitis E in France: Description of Seven Patients with Acute Hepatitis E and Encephalopathy","volume":"14","author":"Bureau","year":"2007","journal-title":"J. Viral Hepat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a031872","DOI":"10.1101\/cshperspect.a031872","article-title":"Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment","volume":"9","author":"Kamar","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.jhep.2022.05.006","article-title":"Chronic Hepatitis E: Advancing Research and Patient Care","volume":"77","author":"Ma","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1700517","DOI":"10.2807\/1560-7917.ES.2018.23.41.1700517","article-title":"Hepatitis E in Italy: 5 Years of National Epidemiological, Virological and Environmental Surveillance, 2012 to 2016","volume":"23","author":"Alfonsi","year":"2018","journal-title":"Eurosurveillance"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Garbuglia, A.R., Koja, G., Villano, U., Minosse, C., Equestre, M., Pauciullo, S., Coppola, A., Madonna, E., Picchi, G., and Di Biase, J. (2024). HEV-3 Subtypes and Strains Detected in Cases of HEV Infection in Central Italy from 2015 to 2023. Infection.","DOI":"10.1007\/s15010-024-02348-0"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3126419","DOI":"10.1155\/2023\/3126419","article-title":"High Prevalence and Genetic Heterogeneity of Genotype 3 Hepatitis E Virus in Wild Boar in Umbria, Central Italy","volume":"2023","author":"Beikpour","year":"2023","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1099\/jgv.0.001435","article-title":"Update: Proposed Reference Sequences for Subtypes of Hepatitis E Virus (Species Orthohepevirus A)","volume":"101","author":"Smith","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ijfoodmicro.2015.09.013","article-title":"Detection of Hepatitis E Virus RNA in Raw Sausages and Liver Sausages from Retail in Germany Using an Optimized Method","volume":"215","author":"Szabo","year":"2015","journal-title":"Int. J. Food Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.fm.2019.02.005","article-title":"Quantification and Genetic Diversity of Hepatitis E Virus in Wild Boar (Sus scrofa) Hunted for Domestic Consumption in Central Italy","volume":"82","author":"Iaconelli","year":"2019","journal-title":"Food Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12985-021-01714-w","article-title":"Hepatitis E Virus Infection in a Patient with Alcohol Related Chronic Liver Disease: A Case Report of Acute-on-Chronic Liver Failure","volume":"18","author":"Fantilli","year":"2021","journal-title":"Virol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/apt.13938","article-title":"Investigation of Underlying Comorbidities as Risk Factors for Symptomatic Human Hepatitis E Virus Infection","volume":"45","author":"Zhang","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","article-title":"Hepatitis E Virus Infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_24","unstructured":"European Centre for Disease Prevention (2017). Hepatitis E in the EU\/EEA, 2005\u20132015, ECDC."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Abravanel, F., Vignon, C., Mercier, A., Gaumery, J.-B., Biron, A., Filisetti, C., Goujart, M.-A., Colot, J., Chamillard, X., and Demortier, J. (2024). Large-Scale HEV Genotype 3 Outbreak on New Caledonia Island. Hepatology.","DOI":"10.1097\/HEP.0000000000001081"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-99-1304-6_1","article-title":"Hepatitis E Virus","volume":"Volume 1417","author":"Wang","year":"2023","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Borghi, M., Pierboni, E., Primavilla, S., Scoccia, E., Costantini, C., Suffredini, E., Graziani, A., Macellari, P., Macr\u00ec, S., and Farneti, S. (2024). Detection of Hepatitis E Virus in Game Meat (Wild Boar) Supply Chain in Umbria Region, Central Italy. Foods, 13.","DOI":"10.3390\/foods13162504"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.jhep.2018.03.005","article-title":"EASL Clinical Practice Guidelines on Hepatitis E Virus Infection","volume":"68","author":"Dalton","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_29","unstructured":"(2024, April 17). Epidemiologia\u2014Dati SEIEVA. Available online: https:\/\/www.Epicentro.Iss.It\/Epatite\/Dati-Seieva#e."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:43:25Z","timestamp":1760114605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,30]]},"references-count":29,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["v16121869"],"URL":"https:\/\/doi.org\/10.3390\/v16121869","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,11,30]]}}}