{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T04:09:31Z","timestamp":1751083771493,"version":"3.41.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T00:00:00Z","timestamp":1514332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI068634","UM1 AI068636","UM1 AI106701"],"award-info":[{"award-number":["UM1 AI068634","UM1 AI068636","UM1 AI106701"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK098079","AI082630"],"award-info":[{"award-number":["DK098079","AI082630"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005347","name":"American Association for the Study of Liver Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>)\u2010free direct\u2010acting antiviral agents (<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>s) have revolutionized chronic hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) treatment; early studies suggest excellent efficacy in acute<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>. However, changes in innate immune responses during<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>therapy for acute<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>are unknown. We studied interferon\u2010stimulated gene (<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>) expression and related cytokines\/chemokines in<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected patients with acute<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>receiving sofosbuvir plus ribavirin (<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">RBV<\/jats:styled-content>) as part of the A5327 clinical trial.<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>expression was determined from<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s, and circulating cytokines\/chemokines were quantified from serum from study participants. The overall sustained virologic response (<jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>) was 57%; all treatment failures were due to virologic relapse. Apart from<jats:italic><jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>2a<\/jats:italic>, baseline<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>\/chemokine\/cytokine levels were similar irrespective of treatment outcome. Downregulation of<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>s was observed at treatment week four and end of treatment (<jats:styled-content style=\"fixed-case\">EOT<\/jats:styled-content>), implicating<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>in establishing elevated<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>s early during<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>infection. Levels of many of these<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>s increased at post\u2010treatment week 12 (<jats:styled-content style=\"fixed-case\">PTW<\/jats:styled-content>12) in relapsers only, coinciding with recurrent<jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content>. Eleven<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>s were differentially expressed in responders vs relapsers. On\u2010treatment viral suppression was also associated with a reduction in<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>\u201010,<jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>11 and<jats:styled-content style=\"fixed-case\">MIP<\/jats:styled-content>\u20101\u03b2 levels. In contrast, circulating<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b1 levels were significantly higher at<jats:styled-content style=\"fixed-case\">EOT<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">PTW<\/jats:styled-content>12 in responders vs relapsers. Upregulation of peripheral<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>expression is established early in the course of<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>infection during acute<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>infection, but did not predict subsequent treatment outcome with<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">RBV<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">ISG<\/jats:styled-content>s were downregulated during therapy and increased post\u2010therapy in relapsers.<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b1 levels were higher in responders at<jats:styled-content style=\"fixed-case\">EOT<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PTW<\/jats:styled-content>12, suggesting that impaired type I<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>production\/secretion may contribute to relapse.<\/jats:p>","DOI":"10.1111\/jvh.12836","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T17:37:19Z","timestamp":1511977039000},"page":"465-472","source":"Crossref","is-referenced-by-count":15,"title":["<scp>IFN<\/scp>\u2010free therapy is associated with restoration of type I<scp>IFN<\/scp>response in<scp>HIV<\/scp>\u20101 patients with acute<scp>HCV<\/scp>infection who achieve<scp>SVR<\/scp>"],"prefix":"10.1111","volume":"25","author":[{"given":"C.","family":"Carlton\u2010Smith","sequence":"first","affiliation":[{"name":"Gastrointestinal Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-4904","authenticated-orcid":false,"given":"J. A.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA"},{"name":"Department of Gastroenterology St Vincent's Hospital University of Melbourne Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Naggie","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Duke University Medical Center Durham NC USA"},{"name":"Duke Clinical Research Institute Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lidofsky","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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