{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:24:14Z","timestamp":1773163454277,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"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\/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":["Liver International"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Direct\u2010acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA therapy is common, little is known about the intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of the gut microbiome and the liver after SVR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010two HCV patients were evaluated before and 9\u2009months after 12\u2009weeks of sofosbuvir\/velpatasvir treatment. All achieved SVR. A liver biopsy, portal blood (direct portal vein cannulation), peripheral blood and stool samples were obtained. RNA\u2010seq and immunofluorescent staining were performed on liver biopsies. RNA\u2010seq and 16S rRNA metagenomics were performed on stool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differential expression within liver transcription showed 514 downregulated genes (FDR <jats:italic>q<\/jats:italic>\u2009&lt;\u2009.05; foldchange &gt;\u20092) enriched in inflammatory pathways; of note, GO:0060337, type 1 IFN signalling (<jats:italic>p<\/jats:italic>\u2009=\u20098e\u201023) and GO:0042742, defence response to bacterium (<jats:italic>p<\/jats:italic>\u2009=\u20098e\u20103). Interestingly, microbial products increased in the portal blood and liver after SVR. Due to the increase in microbial products, the gut microbiome was investigated. There was no dysbiosis by Shannon diversity index or Bacteroides\/Firmicutes ratio. There was a differential increase in genes responsible for bacterial lipopolysaccharide production after SVR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The decrease in the antiviral interferon pathway expression was expected after SVR; however, there was an unanticipated decrease in the transcription of genes involved in recognition and response to bacteria, which was associated with increased levels of microbial products. Finally, the alterations in the function of the gut microbiome are a promising avenue for further investigation of the gut\u2010liver axis, especially in the context of the significant immunological changes noted after SVR.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15737","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T06:24:47Z","timestamp":1695795887000},"page":"2701-2712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non\u2010selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-8778","authenticated-orcid":false,"given":"Gabriella","family":"Quinn","sequence":"first","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabab O.","family":"Ali","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-9439","authenticated-orcid":false,"given":"Kareen","family":"Hill","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3102-8033","authenticated-orcid":false,"given":"Elizabeth","family":"Townsend","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Umarova","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moumita","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine Clinical Center, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shakuntala","family":"Rampertaap","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine Clinical Center, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Schoenfeld","sequence":"additional","affiliation":[{"name":"NIH Clinical Center National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanna","family":"Yang","sequence":"additional","affiliation":[{"name":"NIH Clinical Center National Institutes of Health  Bethesda Maryland 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