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We compared gene profiles of hepatocellular carcinoma (HCC) between HCV\u2010SVR, steatotic liver disease (SLD), and HCV\u2010non\u2010SVR patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV\u2010SVR (<jats:italic>n<\/jats:italic>\u00a0=\u00a022), HCV\u2010non\u2010SVR (<jats:italic>n<\/jats:italic>\u00a0=\u00a056), and SLD (<jats:italic>n<\/jats:italic>\u00a0=\u00a048). Deep sequencing of 2910 hotspots in 55 cancer\u2010related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The HCV\u2010SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.008), were obese (54.5% vs. 17.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002), and had dyslipidemia (18.2% vs. 3.6%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.029) and hyperuricemia (18.2% vs. 3.6%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.029) than the HCV\u2010non\u2010SVR group. Mutational profiling of the HCV\u2010SVR HCC showed significantly lower alteration rates of <jats:italic>AXIN1<\/jats:italic> (13.6% vs. 42.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.016), <jats:italic>ARID2<\/jats:italic> (9.1% vs. 39.3%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.013), and <jats:italic>TP53<\/jats:italic> (9.1% vs. 32.1%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.030) than HCV\u2010non\u2010SVR patients. Compared with HCV\u2010non\u2010SVR\u2010HCC, SLD\u2010HCCs showed significantly lower rates of <jats:italic>TERT<\/jats:italic> promoter mutations (62.5% vs. 85.7%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.004), <jats:italic>ARID2<\/jats:italic> alterations (12.5% vs. 39.3%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.003), and <jats:italic>AXIN1<\/jats:italic> alterations (12.5% vs. 42.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002). HCV\u2010SVR\/MASH\/MASLD\/ALD\u2010HCC had significantly lower alteration rates of the Wnt\/\u03b2\u2010catenin (41.4% vs. 60.7%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.048) and chromatin remodeling pathways (27.1% vs. 48.2%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.026) than HCV\u2010non\u2010SVR\u2010HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HCV\u2010SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD\u2010HCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.14214","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T10:42:41Z","timestamp":1748342561000},"page":"1193-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic alterations in hepatocellular carcinoma after sustained virological response in relation to the molecular characterization of metabolic diseases"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2173-8681","authenticated-orcid":false,"given":"Fukiko","family":"Kawai\u2010Kitahata","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-0064","authenticated-orcid":false,"given":"Yasuhiro","family":"Asahina","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sei","family":"Kakinuma","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Laboratory Science Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Inada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Mochida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiya","family":"Watakabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsubasa","family":"Nobusawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Institute of Science Tokyo  Tokyo 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