{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:33:05Z","timestamp":1762756385123,"version":"build-2065373602"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021089","name":"Moody Endowment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background &amp;amp; aims<\/jats:title>\n                    <jats:p>Direct-acting antivirals (DAAs) revolutionized hepatitis C (HCV) treatment. Yet, some patients present with persistent inflammation and still face adverse outcomes, including cirrhosis and hepatocellular carcinoma, despite achieving sustained virologic response (SVR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach &amp;amp; results<\/jats:title>\n                    <jats:p>This study examined liver biopsies from 22 patients before and after DAA treatment to assess gene and protein expression changes linked to disease progression. Pre-treatment, patients exhibited two distinct profiles: one characterized by high pro-inflammatory and antiviral gene expression (pre-hot), and another with weaker expression (pre-cold). Patients with pre-hot profiles were initially associated with poor outcomes (OR\u00a0=\u00a014.0, 95% CI: 1.31\u2013178.5; p = 0.049), but this lost significance after adjusting for baseline disease severity (adjusted OR\u00a0=\u00a08.04, 95% CI: 0.18\u20132123.07; p = 0.328). Baseline modified hepatitis activity index (MHAI) scores (OR\u00a0=\u00a01.90, 95% CI: 0.72\u20136.34) and fibrosis stage (OR\u00a0=\u00a01.65, 95% CI: 0.44\u20139.97) trended toward predicting poor outcomes but were not significant. Post-treatment, liver enzymes decreased, inflammatory scores improved, and type I interferon pathways were restored, yet 14 of 17 patients (82.3%, 95% CI: 64.2\u2013100%) retained persistent lymphocytic infiltrates. In parallel, spectral imaging further revealed post-treatment shifts in macrophage populations, with a significant decrease in inflammatory subsets (CD14+, CD14+\/Mac387+, p&amp;lt;0.05) and an increase in anti-inflammatory subsets (CD16+, CD16+\/CD163+, CD16+\/CD68+, p&amp;lt;0.05). Analysis of T cell\u2013related marker expression before and after treatment shows that mixed lymphocytic infiltration (CD3+, CD4+, CD8+, CD45RO+) persists within the liver despite viral clearance, with high inter-patient variability likely limiting statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Even after achieving SVR and normalization of gene expression, the liver retained a heterogeneous T cell infiltrate, suggesting that persistent immune activity could continue to influence the risk of adverse outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1662184","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:29:31Z","timestamp":1762756171000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the liver microenvironment following successful therapy for HCV: gene expression profiling and residual T cell infiltration"],"prefix":"10.3389","volume":"15","author":[{"given":"Daniel E.","family":"Millian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban","family":"Arroyave","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G.","family":"Wanninger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santhoshi","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared R.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arvind","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Spratt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique R.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellen","family":"Henning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather L.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar A.","family":"Saldarriaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1007\/s12072-018-9896-4","article-title":"A changing paradigm: management and treatment of the HCV\/HIV-co-infected patient","volume":"12","author":"Abutaleb","year":"2018","journal-title":"Hepatol. 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