{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:13:39Z","timestamp":1784855619113,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defence Translational Team Science Award","doi-asserted-by":"publisher","award":["W81XWH-20-1-0512"],"award-info":[{"award-number":["W81XWH-20-1-0512"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defence Translational Team Science Award","doi-asserted-by":"publisher","award":["W81XWH-20-1-0513"],"award-info":[{"award-number":["W81XWH-20-1-0513"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defence Translational Team Science Award","doi-asserted-by":"publisher","award":["W81XWH-20-1-0514"],"award-info":[{"award-number":["W81XWH-20-1-0514"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Durham VA Medical Center"},{"DOI":"10.13039\/100006510","name":"Duke University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006510","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Statins have been associated with a reduced risk of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC). However, the optimal use for effective protection and whether benefits vary by patient characteristics remain unclear. We evaluated the association between statin use and PLC risk in metabolic-dysfunction-associated steatotic liver disease (MASLD), considering cumulative exposure and potential effect modifiers. Methods: We conducted a retrospective cohort study using the Veteran Affairs electronic health records. Patients with chronically elevated liver enzymes and metabolic dysfunction, without other chronic liver diseases, were identified between 2007 and 2009 and followed through 2019 for incident PLC. Statin exposure was assessed at baseline and during the follow-up, with dose standardization by LDL-lowering potency (simvastatin-equivalent units). Time to PLC was analyzed using Cox models adjusted for covariates, considering potential interactions. Results: Among 329,577 patients (92% male; median age 62 years), 0.82% developed PLC (median follow-up of 9.7 years). Baseline statin use showed a significantly lower PLC risk (adjusted hazard ratio 0.64; 95% CI, 0.57\u20130.71; p &lt; 0.0001). No significant interaction was observed with age, sex, metabolic syndrome, or cirrhosis. Higher cumulative statin exposure demonstrated a dose-dependent risk reduction, remaining significant at simvastatin-equivalent doses &gt; 15,561 mg annually after accounting for incident cirrhosis. Atorvastatin\/rosuvastatin use provided comparable protection, despite different lipophilicity, and demonstrated stronger effects than others. Conclusions: In MASLD, statin therapy was associated with a dose-dependent PLC risk reduction. High-intensity therapy (simvastatin-equivalent &gt; 40 mg daily) conferred substantial protection regardless of age, sex, insulin resistance, or cirrhosis, supporting a potential statin-based PLC chemoprevention in MASLD.<\/jats:p>","DOI":"10.3390\/cancers18071132","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:09:21Z","timestamp":1775038161000},"page":"1132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Statin Use with Reduced Primary Liver Cancer Risk, Independent of Age and Cirrhosis Protection in MASLD"],"prefix":"10.3390","volume":"18","author":[{"given":"Georgia Sofia","family":"Karachaliou","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA"},{"name":"Geriatrics Research Education and Clinical Center (GRECC), VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Dorn","sequence":"additional","affiliation":[{"name":"Health Services Research, VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4260-2707","authenticated-orcid":false,"given":"Ruth M.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Health Services Research, VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA"},{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Arnold","sequence":"additional","affiliation":[{"name":"Human Systems Integration, Office of Clinical Informatics, Office of Health Informatics, Digital Health Office, Veterans Health Administration, Washington, DC 20240, USA"},{"name":"College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa R.","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Center for Advanced Resonance Developmental, Duke University, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-5111","authenticated-orcid":false,"given":"Jimmy T.","family":"Efird","sequence":"additional","affiliation":[{"name":"VA Cooperative Studies Program, Coordinating Center, Boston, MA 02130, USA"},{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal F.","family":"Abdelmalek","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Mae","family":"Diehl","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1824-1067","authenticated-orcid":false,"given":"Ayako","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Division of Gastroenterology, Durham VA Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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