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In contrast, we hypothesized that early DAA treatment of acute hepatitis C virus (HCV) with DAAs may normalize most SIMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we made use of a unique cohort of acute symptomatic hepatitis C patients who cleared HCV with a 6-week course of ledipasvir\/sofosbuvir. Plasma samples were used for proximity extension assay measuring 92 proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Profound SIM alterations were observed in acute HCV patients, with marked upregulation of interleukin (IL)-6 and CXCL-10, whereas certain mediators were downregulated (eg, monocyte chemoattractant protein-4, IL-7). During treatment and follow-up, the majority of SIMs decreased but not all normalized (eg, CDCP1, IL-18). Of note, SIMs that were downregulated before DAA treatment remained suppressed, whereas others that were initially unchanged declined to lower values during treatment and follow-up (eg, CD244).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Acute hepatitis C was associated with marked changes in the soluble inflammatory milieu compared with both chronic hepatitis patients and healthy controls. Whereas early DAA treatment partly normalized this altered signature, long-lasting imprints of HCV remained.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiab048","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T20:12:46Z","timestamp":1611864766000},"page":"441-452","source":"Crossref","is-referenced-by-count":22,"title":["Long-Lasting Imprint in the Soluble Inflammatory Milieu Despite Early Treatment of Acute Symptomatic Hepatitis C"],"prefix":"10.1093","volume":"226","author":[{"given":"Tanvi","family":"Khera","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany"},{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, HepNet Study-House, German Liver Foundation , Hannover , 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