{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:11:01Z","timestamp":1762341061329,"version":"3.41.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Southwest Liver Unit, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth, UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>A minority of injecting drug users, termed exposed uninfected, are resistant to hepatitis C (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection despite repeated low\u2010dose exposures. We identify for the first time a cohort of blood recipients who remained uninfected despite large\u2010dose exposure to<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010contaminated blood and characterize immune factors that may confer protection. Of 1340 blood recipients from the English Look Back database who were transfused<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010contaminated blood, we identified 8 who remained uninfected. In these 8 exposed uninfecteds, we characterized their natural killer (<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>) cell populations and<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010specific T\u2010cell responses. Findings were compared with 10 spontaneous resolvers of<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>infection, 10 patients with chronic<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>infection and 10 healthy controls. Exposed uninfecteds had significantly greater numbers of<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>cells with the activating receptor<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>p30+ on<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>bright<\/jats:sup>and<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup>subsets compared with other groups (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Following interleukin\u20102 activation,<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>cells of exposed uninfecteds had enhanced cytotoxicity that positively correlated with<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>p30 expression (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.02). Differences in<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>p80 and<jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">DL<\/jats:styled-content>3 expression were also observed.<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010specific T\u2010cell responses were observed in some exposed uninfecteds but of low amplitude. Exposure without infection following transfusion of<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010contaminated blood is a very rare phenomenon and suggests a high level of resistance to infection. Enhanced<jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>cell activation and killing, with weak<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010specific T\u2010cell responses, were observed many years after exposure in uninfected recipients and may contribute to protection from<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>acquisition, although additional protective factors are being sought in this important cohort.<\/jats:p>","DOI":"10.1111\/jvh.12810","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T05:46:36Z","timestamp":1508823996000},"page":"245-253","source":"Crossref","is-referenced-by-count":4,"title":["Enhanced natural killer cell activity is found in exposed uninfected recipients of hepatitis C\u2010contaminated blood"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-3222","authenticated-orcid":false,"given":"M. M.","family":"Ow","sequence":"first","affiliation":[{"name":"Department of Medicine University of Auckland Auckland New Zealand"},{"name":"Hepatology Research Group Plymouth University Peninsula Schools of Medicine and Dentistry Plymouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Hepatology Research Group Plymouth University Peninsula Schools of Medicine and Dentistry Plymouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U. M.","family":"Warshow","sequence":"additional","affiliation":[{"name":"Hepatology Research Group Plymouth University Peninsula Schools of Medicine and Dentistry Plymouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. E.","family":"Cramp","sequence":"additional","affiliation":[{"name":"Hepatology Research Group Plymouth University Peninsula Schools of Medicine and Dentistry Plymouth UK"},{"name":"Southwest Liver Unit Derriford Hospital Plymouth Hospitals NHS Trust Plymouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1002\/hep.1840360706","article-title":"Natural history of chronic hepatitis C","volume":"36","author":"Seeff LB","year":"2002","journal-title":"Hepatology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39133"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00319.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq121"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/593337"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23896"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.04.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/422605"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/589510"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2008.01016.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.05.014"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.05.013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23477"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.04.005"},{"key":"e_1_2_8_18_1","first-page":"1","article-title":"Exploration of potential mechanisms of hepatitis C virus resistance in exposed uninfected intravenous drug users","author":"Shawa IT","year":"2017","journal-title":"J Viral Hepat."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.212555"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02332.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2011.01574.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/517279"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12252-12258.2004"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-9-76"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/516546"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200101)31:1<233::AID-IMMU233>3.0.CO;2-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097670"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.23.11392-11400.2001"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21081"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/75063"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12810","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T18:09:53Z","timestamp":1750961393000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,20]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/jvh.12810"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12810","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"type":"print","value":"1352-0504"},{"type":"electronic","value":"1365-2893"}],"subject":[],"published":{"date-parts":[[2017,11,20]]}}}