{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:13:50Z","timestamp":1784855630925,"version":"3.55.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Lipophilic but not hydrophilic statins have been shown to be associated with reduced risk for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. We investigated differential actions of lipophilic and hydrophilic statins and their ability to modulate a clinical prognostic liver signature (PLS) predicting HCC risk in patients with liver disease. Hepatitis C virus (HCV)\u2013infected Huh7.5.1 cells, recently developed as a model to screen HCC chemopreventive agents, were treated with lipophilic statins (atorvastatin and simvastatin) and hydrophilic statins (rosuvastatin and pravastatin), and then analyzed by RNA sequencing and PLS. Lipophilic statins, particularly atorvastatin, more significantly suppressed the HCV\u2010induced high\u2010risk pattern of PLS and genes in YAP and AKT pathway implicated in fibrogenesis and carcinogenesis, compared with the hydrophilic statins. While atorvastatin inhibited YAP activation through the mevalonate pathway, the distinctive AKT inhibition of atorvastatin was mediated by stabilizing truncated retinoid X receptor alpha, which has been known to enhance AKT activation, representing a target for HCC chemoprevention. In addition, atorvastatin modulated the high\u2010risk PLS in an <jats:italic toggle=\"yes\">in vitro<\/jats:italic> model of nonalcoholic fatty liver disease (NAFLD). <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Atorvastatin distinctively inhibits YAP and AKT activation, which are biologically implicated in HCC development, and attenuates a high\u2010risk PLS in an <jats:italic toggle=\"yes\">in vitro<\/jats:italic> model of HCV infection and NAFLD. These findings suggest that atorvastatin is the most potent statin to reduce HCC risk in patients with viral and metabolic liver diseases.<\/jats:p>","DOI":"10.1002\/hep4.1991","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T06:51:45Z","timestamp":1655448705000},"page":"2581-2593","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":30,"title":["Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature"],"prefix":"10.1097","volume":"6","author":[{"given":"Myung\u2010Ho","family":"Kim","sequence":"first","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"},{"name":"Department of Gastroenterology,CHA Bundang Medical Center,CHA University School of Medicine,Seongnam,South Korea"},{"name":"Department of Gastroenterology, Chaum Life Center,CHA University School of Medicine,Seoul,South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Salloum","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongqi","family":"Qian","sequence":"additional","affiliation":[{"name":"Liver Tumor Translational Research Program,Simmons Comprehensive Cancer Center,Division of Digestive and Liver Diseases,Department of Internal Medicine,University of Texas Southwestern Medical Center,Dallas,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai Ping","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology,Massachusetts General Hospital,Boston,Massachusetts,USA"},{"name":"Department of Genetics,Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojin","family":"Lee","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuti G.","family":"Shroff","sequence":"additional","affiliation":[{"name":"Department of Pathology,Massachusetts General Hospital and Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan I.","family":"Sadreyev","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology,Massachusetts General Hospital,Boston,Massachusetts,USA"},{"name":"Department of Pathology,Massachusetts General Hospital and Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-7264","authenticated-orcid":false,"given":"Kathleen E.","family":"Corey","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Baumert","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,U1110,Institut de Recherche sur les Maladies Virales et H\u00e9patiques,Strasbourg,France"},{"name":"Pole Hepato\u2010digestif, IHU,Strasbourg University Hospitals,Strasbourg,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Hoshida","sequence":"additional","affiliation":[{"name":"Liver Tumor Translational Research Program,Simmons Comprehensive Cancer Center,Division of Digestive and Liver Diseases,Department of Internal Medicine,University of Texas Southwestern Medical Center,Dallas,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"Chung","sequence":"additional","affiliation":[{"name":"Liver Center,Gastrointestinal Division,Massachusetts General Hospital,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"hep41991-bib-0001-20241118","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/hep.27969","article-title":"World\u2010wide 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