{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:14:07Z","timestamp":1793060047153,"version":"4.5.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner\u2013Fresenius\u2013Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case description<\/jats:title>\n                    <jats:p>A 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient\u2019s neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient\u2019s neurological status improved after the administration of intravenous immunoglobulins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1445944","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:27:18Z","timestamp":1721953638000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic hepatitis E virus-induced spinal cord atrophy in a patient with chronic lymphatic leukemia: a case report and interdisciplinary management proposal"],"prefix":"10.3389","volume":"15","author":[{"given":"Marvin","family":"Ritter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaposi","family":"Yomade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben-Ole","family":"Holtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Deinhardt-Emmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron Lawson","family":"McLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hartinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Bechwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Huss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mawrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertus","family":"Axer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin G.","family":"Schrenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Reuken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"M\u00e4urer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3390\/v8080211","article-title":"Hepatitis E seroprevalence in europe: A meta-analysis","volume":"8","author":"Hartl","year":"2016","journal-title":"Viruses"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.04.022","article-title":"The burden of hepatitis E among patients with haematological Malignancies: A retrospective European cohort study","volume":"71","author":"von Felden","year":"2019","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02286.x","article-title":"Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients","volume":"8","author":"Kamar","year":"2008","journal-title":"Am J Transplant"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.005","article-title":"Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection","volume":"68","year":"2018","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.08.020","article-title":"Hepatitis E virus infection in cancer patients","volume":"28","author":"Chiu","year":"2022","journal-title":"Transplant Cell Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280853","article-title":"Clinical features of hepatitis E infections in patients with hematologic disorders","volume":"107","author":"Ghandili","year":"2022","journal-title":"Haematologica"},{"key":"B8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/medsci8010009","article-title":"Gajendran M. A systematic review of the extra-hepatic manifestations of hepatitis E virus infection","volume":"8","author":"Rawla","year":"2020","journal-title":"Med Sci (Basel)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3201\/eid1702.100856","article-title":"Hepatitis E virus and neurologic disorders","volume":"17","author":"Kamar","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12986","article-title":"Extra-hepatic manifestations of autochthonous hepatitis E infection","volume":"40","author":"Woolson","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000643","article-title":"Neurologic complications of acute hepatitis E virus infection","volume":"7","author":"Ripellino","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000939","article-title":"Evidence for independent hepatitis E virus replication in the brain","volume":"8","author":"den Drijver","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nrneurol.2015.234","article-title":"Hepatitis E virus and neurological injury","volume":"12","author":"Dalton","year":"2016","journal-title":"Nat Rev Neurol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.3390\/pharmaceutics13081126","article-title":"Evaluation of ribavirin\u2013poloxamer microparticles for improved intranasal absorption","volume":"13","author":"Vasa","year":"2021","journal-title":"Pharmaceutics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.jinf.2021.07.021","article-title":"Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms","volume":"83","author":"Wu","year":"2021","journal-title":"J Infect"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.3390\/cells10092281","article-title":"Hepatitis E virus infection-immune responses to an underestimated global threat","volume":"10","author":"Kupke","year":"2021","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2201862119","article-title":"Hepatitis E virus infects brain microvascular endothelial cells, crosses the blood-brain barrier, and invades the central nervous system","volume":"119","author":"Tian","year":"2022","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12515","article-title":"Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells","volume":"23","author":"Drave","year":"2016","journal-title":"J Viral Hepat"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5695","article-title":"Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity","volume":"12","author":"Mohn","year":"2023","journal-title":"Cancer Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3000605231187941","DOI":"10.1177\/03000605231187941","article-title":"Early ribavirin for hepatitis E virus infection in patients receiving immunosuppressive therapy: a retrospective, observational study","volume":"51","author":"Franz","year":"2023","journal-title":"J Int Med Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"ofz345","DOI":"10.1093\/ofid\/ofz345","article-title":"Ribavirin for chronic hepatitis E virus infection in ibrutinib-exposed patients","volume":"6","author":"Protin","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3390\/pathogens8030129","article-title":"Chronic hepatitis E virus infection during lymphoplasmacytic lymphoma and ibrutinib treatment","volume":"8","author":"Schlevogt","year":"2019","journal-title":"Pathogens"},{"key":"B24","doi-asserted-by":"publisher","first-page":"17185","DOI":"10.3390\/ijms242417185","article-title":"In-host HEV quasispecies evolution shows the limits of mutagenic antiviral treatments","volume":"24","author":"Colomer-Castell","year":"2023","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1445944\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:27:22Z","timestamp":1721953642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1445944\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":24,"alternative-id":["10.3389\/fimmu.2024.1445944"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1445944","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1445944"}}