{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:22:27Z","timestamp":1740126147396,"version":"3.37.3"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T00:00:00Z","timestamp":1543795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI121348"],"award-info":[{"award-number":["K08AI121348"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM103331"],"award-info":[{"award-number":["P30GM103331"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2019,3]]},"abstract":"Summary<\/jats:title>Treatment of chronic hepatitis C virus (HCV<\/jats:styled-content>) infection with direct\u2010acting antivirals (DAA<\/jats:styled-content>s) results in a sustained virologic response (SVR<\/jats:styled-content>) in most patients. While highly efficacious, ~3%\u20105% of patients do not achieve SVR<\/jats:styled-content> despite having virus that appears susceptible. It is unclear whether host factors contribute to treatment failures, although innate and adaptive immunity may play a role. Previous studies showed that after DAA<\/jats:styled-content> treatment, the composition of intrahepatic immune cells does not normalize relative to healthy volunteers, even in cases where SVR<\/jats:styled-content> is achieved. We used paired pre\u2010 and post\u2010treatment liver biopsies from 13 patients treated with sofosbuvir and ribavirin, 4 of whom relapsed, to analyse intracellular immune changes during DAA<\/jats:styled-content> treatment and explore correlations with inflammation and treatment outcome. We performed single marker immunohistochemistry followed by electronic image capture, manual annotation of parenchymal and non\u2010parenchymal regions, and quantitative image analysis. The predominant cellular change during treatment was a decrease in CD<\/jats:styled-content>8+ cellular density in both parenchymal and non\u2010parenchymal regions. CD<\/jats:styled-content>68+ Kupffer cell density correlated with hepatic inflammation (AST<\/jats:styled-content>, ALT<\/jats:styled-content>) pre\u2010treatment, but did not change during treatment. CD<\/jats:styled-content>4+ cellular density decreased in non\u2010parenchymal regions and, intriguingly, was lower pre\u2010treatment in subjects who eventually relapsed. Other cellular markers (CD<\/jats:styled-content>56, CD<\/jats:styled-content>20), as well as markers of apoptosis (TIA<\/jats:styled-content>\u20101) and activated stellate cells, did not change significantly during treatment or differ by treatment outcome. The predominant intrahepatic cellular change during DAA<\/jats:styled-content> treatment of chronic HCV<\/jats:styled-content> infection is a reduction in CD<\/jats:styled-content>8+ cellular density, but this did not correlate with treatment outcome.<\/jats:p>","DOI":"10.1111\/jvh.13034","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T16:28:56Z","timestamp":1541089736000},"page":"323-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of changes in intrahepatic immune cell populations during HCV<\/scp> treatment with sofosbuvir and ribavirin"],"prefix":"10.1111","volume":"26","author":[{"given":"Cody","family":"Orr","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases Medical University of South Carolina Charleston South 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