{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:04:40Z","timestamp":1792065880272,"version":"4.4.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis. Eventually, let\u20107a\/7c\/7d\u20105p and miR\u2010122\u20105p were identified as candidate predictors of disease progression. Cross\u2010sectional analyses at the time of initial liver biopsy showed that reduced levels of let\u20107a\/7c\/7d\u20105p (let\u20107s) in plasma were correlated with advanced histological hepatic fibrosis stage and other fibrotic markers, whereas miR\u2010122\u20105p levels in plasma were positively correlated with inflammatory activity, but not fibrosis. Measuring let\u20107s levels in EVs was not superior to intact plasma for discriminating significant hepatic fibrosis. Longitudinal analyses in 60 patients with paired liver biopsies showed that let\u20107s levels in plasma markedly declined over time in parallel with fibrosis progression. However, circulating let\u20107s levels did not parallel those in the liver. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Of all miRNAs screened, the let\u20107 family showed the best correlation with hepatic fibrosis in CHC. A single determination of let\u20107s levels in plasma did not have superior predictive value for significant hepatic fibrosis compared with that of fibrosis\u20104 index, but the rate of let\u20107s decline in paired longitudinal samples correlated well with fibrosis progression. Pathway analysis suggested that low levels of let\u20107 may influence hepatic fibrogenesis through activation of transforming growth factor \u03b2 signaling in hepatic stellate cells. (H<jats:sc>epatology<\/jats:sc> 2016;64:732\u2010745)<\/jats:p>","DOI":"10.1002\/hep.28660","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T23:58:09Z","timestamp":1464307089000},"page":"732-745","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":92,"title":["Circulating let\u20107 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C"],"prefix":"10.1097","volume":"64","author":[{"given":"Kentaro","family":"Matsuura","sequence":"first","affiliation":[{"name":"Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"},{"name":"Department of Gastroenterology and Metabolism,Nagoya City University Graduate School of Medical Sciences,Nagoya,Japan"},{"name":"Department of Virology and Liver Unit,Nagoya City University Graduate School of Medical Sciences,Nagoya,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Schechterly","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Farci","sequence":"additional","affiliation":[{"name":"Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Virology and Liver Unit,Nagoya City University Graduate School of Medical Sciences,Nagoya,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey J.","family":"Alter","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,7,7]]},"reference":[{"key":"hep28660-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/hep.27826","article-title":"Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: an integrated safety and efficacy 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