{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:48:05Z","timestamp":1792496885956,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T00:00:00Z","timestamp":1702684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as Paslahepevirus balayani, pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. Rocahepevirus ratti, formerly known as Orthohepevirus C, is a single-stranded RNA virus, recently reassigned to Rocahepevirus genus in the Hepeviridae family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295\/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128\/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans.<\/jats:p>","DOI":"10.3390\/microorganisms11122996","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:41:35Z","timestamp":1702878095000},"page":"2996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Rocahepevirus ratti as an Emerging Cause of Acute Hepatitis Worldwide"],"prefix":"10.3390","volume":"11","author":[{"given":"Sara","family":"Benavent","sequence":"first","affiliation":[{"name":"Microbiology Department, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carlos","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Public Health, Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-9753","authenticated-orcid":false,"given":"Gabriel","family":"Reina","sequence":"additional","affiliation":[{"name":"Microbiology Department, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,16]]},"reference":[{"key":"ref_1","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (2023, October 31). Hepatitis Viral, Available online: https:\/\/www.niddk.nih.gov\/health-information\/informacion-de-la-salud\/enfermedades-higado\/hepatitis-viral."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"001778","DOI":"10.1099\/jgv.0.001778","article-title":"ICTV Virus Taxonomy Profile: Hepeviridae 2022","volume":"103","author":"Purdy","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Reuter, G., Boros, \u00c1., and Pankovics, P. (2020). Review of Hepatitis E Virus in Rats: Evident Risk of Species Orthohepevirus C to Human Zoonotic Infection and Disease. Viruses, 12.","DOI":"10.3390\/v12101148"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jhep.2022.01.028","article-title":"Orthohepevirus C Infection as an Emerging Cause of Acute Hepatitis in Spain: First Report in Europe","volume":"77","author":"Frias","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"baaa062","DOI":"10.1093\/database\/baaa062","article-title":"NCBI Taxonomy: A Comprehensive Update on Curation, Resources and Tools","volume":"2020","author":"Schoch","year":"2020","journal-title":"Database"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s12250-018-0011-8","article-title":"Chevrier\u2019s Field Mouse (Apodemus chevrieri) and P\u00e8re David\u2019s Vole (Eothenomys melanogaster) in China Carry Orthohepeviruses That Form Two Putative Novel Genotypes within the Species Orthohepevirus C","volume":"33","author":"Wang","year":"2018","journal-title":"Virol. Sin."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, B., Harms, D., Yang, X.L., and Bock, C.T. (2020). Orthohepevirus C: An Expanding Species of Emerging Hepatitis e Virus Variants. Pathogens, 9.","DOI":"10.3390\/pathogens9030154"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.3201\/eid1609.100444","article-title":"Novel Hepatitis E Virus Genotype in Norway Rats, Germany","volume":"16","author":"Johne","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1159\/000431191","article-title":"Hepatitis e Virus: German Advisory Committee Blood (Arbeitskreis blut), Subgroup \u201cAssessment of Pathogens Transmissible by Blood\u201d","volume":"42","author":"Seitz","year":"2015","journal-title":"Transfus. Med. Hemother."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.csbj.2021.03.038","article-title":"Structural and Molecular Biology of Hepatitis E Virus","volume":"19","author":"Wang","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bai, H., Ami, Y., Suzaki, Y., Doan, Y.H., Muramatsu, M., and Li, T.C. (2023). Open Reading Frame 4 Is Not Essential in the Replication and Infection of Genotype 1 Hepatitis E Virus. Viruses, 15.","DOI":"10.3390\/v15030784"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Capai, L., Charrel, R., and Falchi, A. (2018). Hepatitis e in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps?. Viruses, 10.","DOI":"10.3390\/v10060285"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1007\/s00705-022-05575-8","article-title":"Structural Aspects of Hepatitis E Virus","volume":"167","author":"Cancela","year":"2022","journal-title":"Arch. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Faber, M., Wenzel, J.J., Erl, M., Stark, K., and Schemmerer, M. (2022). No Evidence for Orthohepevirus C in Archived Human Samples in Germany, 2000\u20132020. Viruses, 14.","DOI":"10.3390\/v14040742"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104284","DOI":"10.1016\/j.jcv.2020.104284","article-title":"Four-Year Long (2014\u20132017) Clinical and Laboratory Surveillance of Hepatitis E Virus Infections Using Combined Antibody, Molecular, Antigen and Avidity Detection Methods: Increasing Incidence and Chronic HEV Case in Hungary","volume":"124","author":"Pankovics","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/cid\/ciab919","article-title":"Hepatitis e Virus Species C Infection in Humans, Hong Kong","volume":"75","author":"Sridhar","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/hep.31138","article-title":"Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis","volume":"73","author":"Sridhar","year":"2021","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.3201\/eid2412.180937","article-title":"Rat Hepatitis E Virus as Cause of Persistent Hepatitis after Liver Transplant","volume":"24","author":"Sridhar","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/infdis\/jiz025","article-title":"Rat Hepatitis e Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient","volume":"220","author":"Andonov","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"726363","DOI":"10.3389\/fmed.2021.726363","article-title":"Rat Hepatitis E Virus: Presence in Humans in South-Western France?","volume":"8","author":"Parraud","year":"2021","journal-title":"Front. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1016\/j.jhep.2023.02.008","article-title":"Orthohepevirus C Hepatitis, an Underdiagnosed Disease?","volume":"79","author":"Rodriguez","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3201\/eid1901.121007","article-title":"Characterization of Full Genome of Rat Hepatitis E Virus Strain from Vietnam","volume":"19","author":"Li","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00430-011-0221-2","article-title":"Seroprevalence Study in Forestry Workers from Eastern Germany Using Novel Genotype 3- and Rat Hepatitis E Virus-Specific Immunoglobulin G ELISAs","volume":"201","author":"Dremsek","year":"2012","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1292\/jvms.16-0200","article-title":"Serological Evidence of Infection with Rodent-Borne Hepatitis E Virus HEV-C1 or Antigenically Related Virus in Humans","volume":"78","author":"Shimizu","year":"2016","journal-title":"J. Vet. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.jhep.2020.12.028","article-title":"Multimodal Investigation of Rat Hepatitis E Virus Antigenicity: Implications for Infection, Diagnostics, and Vaccine Efficacy","volume":"74","author":"Sridhar","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100793","DOI":"10.1016\/j.jhepr.2023.100793","article-title":"An Immunoassay System to Investigate Epidemiology of Rocahepevirus ratti (Rat Hepatitis E Virus) Infection in Humans","volume":"5","author":"Situ","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e02073-20","DOI":"10.1128\/AEM.02073-20","article-title":"Variations among Viruses in Influent Water and Effluent Water at a Wastewater Plant over One Year as Assessed by Quantitative PCR and Metagenomics","volume":"86","author":"Wang","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e02675-23","DOI":"10.1128\/spectrum.02675-23","article-title":"Surveillance for Rat Hepatitis E in Wastewater Networks, Italy","volume":"11","author":"Palombieri","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168203","DOI":"10.1016\/j.scitotenv.2023.168203","article-title":"Correlation of Hepatitis E and Rat Hepatitis E Viruses Urban Wastewater Monitoring and Clinical Cases","volume":"908","author":"Risalde","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.3201\/eid1712.110482","article-title":"Hepatitis E Virus in Rats, Los Angeles, California, USA","volume":"17","author":"Purcell","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vetmic.2017.07.001","article-title":"Detection of Rat Hepatitis E Virus in Wild Norway Rats (Rattus norvegicus) and Black Rats (Rattus rattus) from 11 European Countries","volume":"208","author":"Ryll","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1099\/vir.0.016584-0","article-title":"Detection of a Novel Hepatitis E-like Virus in Faeces of Wild Rats Using a Nested Broad-Spectrum RT-PCR","volume":"91","author":"Johne","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.meegid.2012.02.021","article-title":"Rat Hepatitis E Virus: Geographical Clustering within Germany and Serological Detection in Wild Norway Rats (Rattus norvegicus)","volume":"12","author":"Johne","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1099\/vir.0.034835-0","article-title":"Characterization of Self-Assembled Virus-like Particles of Rat Hepatitis E Virus Generated by Recombinant Baculoviruses","volume":"92","author":"Li","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.vetmic.2013.03.017","article-title":"High Prevalence of Rat Hepatitis E Virus in Wild Rats in China","volume":"165","author":"Li","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.3201\/eid1808.120070","article-title":"Hepatitis E Virus Genotype 3 in Wild Rats, United States","volume":"18","author":"Lack","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/zph.12581","article-title":"First Detection of Hepatitis E Virus (Orthohepevirus C) in Wild Brown Rats (Rattus norvegicus) from Great Britain","volume":"66","author":"Murphy","year":"2019","journal-title":"Zoonoses Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.3201\/eid2909.230517","article-title":"Rat Hepatitis E Virus in Norway Rats, Ontario, Canada, 2018\u20132021","volume":"29","author":"Robinson","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Porea, D., Raileanu, C., Crivei, L.A., Gotu, V., Savuta, G., and Pavio, N. (2023). First Detection of Hepatitis E Virus (Rocahepevirus ratti Genotype C1) in Synanthropic Norway Rats (Rattus norvegicus) in Romania. Viruses, 15.","DOI":"10.3390\/v15061337"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00705-012-1462-0","article-title":"Frequent Detection and Characterization of Hepatitis E Virus Variants in Wild Rats (Rattus rattus) in Indonesia","volume":"158","author":"Mulyanto","year":"2013","journal-title":"Arch. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.virusres.2013.10.029","article-title":"Marked Genomic Heterogeneity of Rat Hepatitis E Virus Strains in Indonesia Demonstrated on a Full-Length Genome Analysis","volume":"179","author":"Mulyanto","year":"2014","journal-title":"Virus Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00705-018-3736-7","article-title":"The Identification and Characterization of Novel Rat Hepatitis E Virus Strains in Bali and Sumbawa, Indonesia","volume":"163","author":"Primadharsini","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.vetmic.2018.06.014","article-title":"Detection of Rat Hepatitis E Virus, but Not Human Pathogenic Hepatitis E Virus Genotype 1\u20134 Infections in Wild Rats from Lithuania","volume":"221","author":"Simanavicius","year":"2018","journal-title":"Vet. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"198766","DOI":"10.1016\/j.virusres.2022.198766","article-title":"First Detection and Characterization of Rat Hepatitis E Virus (HEV-C1) in Japan","volume":"314","author":"Takahashi","year":"2022","journal-title":"Virus Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wu, Z., Lu, L., Du, J., Yang, L., Ren, X., Liu, B., Jiang, J., Yang, J., Dong, J., and Sun, L. (2018). Comparative Analysis of Rodent and Small Mammal Viromes to Better Understand the Wildlife Origin of Emerging Infectious Diseases. Microbiome, 6.","DOI":"10.1186\/s40168-018-0554-9"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.virol.2018.03.025","article-title":"Novel Orthohepeviruses in Wild Rodents from S\u00e3o Paulo State, Brazil","volume":"519","author":"Romeiro","year":"2018","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1007\/s00705-019-04347-1","article-title":"Genomic and Spatial Variability of a European Common Vole Hepevirus","volume":"164","author":"Ryll","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3201\/eid1908.130069","article-title":"Asian Musk Shrew as a Reservoir of Rat Hepatitis E Virus, China","volume":"19","author":"Guan","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Onyuok, S.O., Hu, B., Li, B., Fan, Y., Kering, K., Ochola, G.O., Zheng, X.S., Obanda, V., Ommeh, S., and Yang, X.L. (2019). Molecular Detection and Genetic Characterization of Novel RNA Viruses in Wild and Synanthropic Rodents and Shrews in Kenya. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02696"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"709","DOI":"10.3201\/eid2004.131815","article-title":"Complete Genome of Hepatitis E Virus from Laboratory Ferrets","volume":"20","author":"Li","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.vetmic.2017.11.005","article-title":"Serological Evidence of Hepatitis E Virus Infection in Zoo Animals and Identification of a Rodent-Borne Strain in a Syrian Brown Bear","volume":"212","author":"Spahr","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lanszki, Z., Kurucz, K., Zeghbib, S., Kemenesi, G., Lanszki, J., and Jakab, F. (2020). Identification of Hepatitis E Virus in the Feces of Red Foxes (Vulpes vulpes). Animals, 10.","DOI":"10.3390\/ani10101841"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/tbed.14437","article-title":"Serological and Molecular Survey of Hepatitis E Virus in Cats and Dogs in Spain","volume":"69","author":"Ulrich","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.meegid.2016.06.013","article-title":"Divergent Hepatitis E Virus in Birds of Prey, Common Kestrel (Falco tinnunculus) and Red-Footed Falcon (F. vespertinus), Hungary","volume":"43","author":"Reuter","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.vetmic.2015.11.014","article-title":"Ferret Hepatitis E Virus Infection Induces Acute Hepatitis and Persistent Infection in Ferrets","volume":"183","author":"Li","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100546","DOI":"10.1016\/j.jhepr.2022.100546","article-title":"A Small Animal Model of Chronic Hepatitis E Infection Using Immunocompromised Rats","volume":"4","author":"Sridhar","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/1751-7915.14247","article-title":"Optimization of the Molecular Diagnosis of the Acute Hepatitis E Virus Infection","volume":"16","author":"Frias","year":"2023","journal-title":"Microb. Biotechnol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/12\/2996\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:39:56Z","timestamp":1760132396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/12\/2996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,16]]},"references-count":58,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["microorganisms11122996"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11122996","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,16]]}}}