{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:23:34Z","timestamp":1788344614377,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000848","name":"University Of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To determine the relative utility of <jats:italic>in\u2010situ<\/jats:italic> testing for hepatitis E virus (<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and paraffin\u2010section polymerase chain reaction (<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>) to diagnose <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> infection in paraffin\u2010embedded clinical liver biopsies, and to correlate with clinicopathological characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We evaluated <jats:italic>in\u2010situ<\/jats:italic> and quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>)\u2010based approaches to identifying <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> in clinical liver biopsies from infected patients from multiple centres, correlating with clinical setting (immunocompetent, allograft or immunosuppressed native liver) and histological findings. Thirty\u2010six biopsies from 29 patients had histological data, 27 and 23 of which had satisfactory material for <jats:italic>in\u2010situ <\/jats:italic><jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> testing and tissue <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>, respectively. Both approaches specifically identified <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> infection, but tissue <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> was significantly more sensitive than RNAscope <jats:italic>in\u2010situ<\/jats:italic> testing (<jats:italic>P<\/jats:italic> = 0.035). In immunocompetent but not immunosuppressed patients the tissue <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> yield correlated with the severity of lobular hepatitis (rho = 0.94, <jats:italic>P<\/jats:italic> &lt; 0.001). <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> viral yield was comparably high in allografts and immunosuppressed native livers and significantly greater than with native liver infection. Immunosuppressed patients showed reduced severity of hepatitis and cholestatic changes, compared with immunocompetent patients. Indeed, <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\u2010infected liver allografts could show minimal hepatitis for many months. In individual cases each technique was useful when serum was not available to identify chronic infection retrospectively (in biopsies taken 4\u201331 months before diagnosis), to identify persistent\/residual infection when contemporary serum <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> was negative and to identify cleared infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> is more effective than <jats:italic>in\u2010situ <\/jats:italic><jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> testing to identify <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> infection in paraffin\u2010embedded liver biopsies and has diagnostic utility in selected settings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13266","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T16:58:15Z","timestamp":1495731495000},"page":"580-590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Detection of viral hepatitis E in clinical liver biopsies"],"prefix":"10.1111","volume":"71","author":[{"given":"Sandrine","family":"Prost","sequence":"first","affiliation":[{"name":"Department of Pathology Royal Infirmary of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L","family":"Crossan","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Glasgow Caledonian University Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry R","family":"Dalton","sequence":"additional","affiliation":[{"name":"European Centre for Environment and Human Health University of Exeter Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"De Man","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nassim","family":"Kamar","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Organ Transplantation Universit\u00e9 Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janick","family":"Selves","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Toulouse Department of Pathology Centre Hospitalier Universitaire de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine","family":"Dhaliwal","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Infirmary of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Scobie","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences Glasgow Caledonian University Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-4080","authenticated-orcid":false,"given":"Christopher O C","family":"Bellamy","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Infirmary of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03504.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.07.051"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60595-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2007.00858.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1702.100856"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12986"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62074-7"},{"key":"e_1_2_7_9_1","first-page":"1","article-title":"Extra\u2010hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature","volume":"4","author":"Bazerbachi F","year":"2016","journal-title":"Gastroenterol. 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