{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:33:36Z","timestamp":1790775216575,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"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":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Genetic factors and steatosis predispose to hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus; however, their impact in patients with cirrhosis cured by direct\u2010acting antivirals (DAAs) is still undefined. We assessed the association between a genetic risk score (GRS) of hepatic fat accumulation, combining variants in <jats:italic toggle=\"yes\">PNPLA3<\/jats:italic> (patatin\u2010like phospholipase domain containing 3), <jats:italic toggle=\"yes\">MBOAT7<\/jats:italic> (membrane bound O\u2010acyltransferase domain containing 7), <jats:italic toggle=\"yes\">TM6SF2<\/jats:italic> (transmembrane 6 superfamily member 2), <jats:italic toggle=\"yes\">GCKR<\/jats:italic> (glucokinase regulator), and HCC in patients treated with DAAs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We considered 509 consecutive patients with HCV cirrhosis (defined histologically or when liver stiffness \u226512\u00a0kPa) treated with DAAs. HCC was diagnosed according to international recommendations. GRS was calculated from the weighted impact of single variants on hepatic fat content quantified by H<jats:sup>1<\/jats:sup> spectrometry in the general population (Dallas Heart Study). During a median follow\u2010up of 43 (3\u201057) months after DAA start, 36 of 452 (8%) patients developed <jats:italic toggle=\"yes\">de novo<\/jats:italic> HCC, 4\u2010year cumulative probability being 9% (95% confidence interval 7%\u201012%). Male sex (hazard ratio [HR] 2.54, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.02), diabetes (HR 2.39, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.01), albumin (HR 0.35, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.001), and GRS score &gt;0.597 (HR 2.30, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.04) were independent predictors of <jats:italic toggle=\"yes\">de novo<\/jats:italic> HCC. In contrast, single genetic risk variants were not useful in stratifying HCC risk. The proportion of patients who developed HCC according to the combination of the independent risk factors ranged from 11% to 67%. HCC recurred in 28 of 57 (49%) patients with previous history; diabetes and ethnicity were the only independent predictors of HCC recurrence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In a large cohort of DAA\u2010treated patients with cirrhotic HCV, GRS was associated with <jats:italic toggle=\"yes\">de novo<\/jats:italic> HCC independently of classical risk factors, including liver disease severity. These data suggest that hepatic fat (i.e., lipotoxicity) promotes HCC in this setting and may represent a target for chemoprevention. Combination of clinical and genetic predictors may improve HCC risk stratification.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31500","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T01:46:02Z","timestamp":1596764762000},"page":"1912-1923","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":62,"title":["Hepatic Fat\u2014Genetic Risk Score Predicts Hepatocellular Carcinoma in Patients With Cirrhotic HCV Treated With DAAs"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-4669","authenticated-orcid":false,"given":"Elisabetta","family":"Degasperi","sequence":"first","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-2401","authenticated-orcid":false,"given":"Enrico","family":"Galmozzi","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pelusi","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Hematology,Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Pathophysiology and Transplantation,University of Milan,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Soffredini","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Borghi","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Perbellini","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"Facchetti","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3493-6504","authenticated-orcid":false,"given":"Massimo","family":"Iavarone","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Sangiovanni","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. Migliavacca\u201d Center for Liver Disease,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-0345","authenticated-orcid":false,"given":"Luca","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Hematology,Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico,Milan,Italy"},{"name":"Department of Pathophysiology and Transplantation,University of Milan,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-7476","authenticated-orcid":false,"given":"Pietro","family":"Lampertico","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology,CRC \u201cA. M. and A. 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