Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes
Open accessAbstract
BACKGROUND & AIMS: Experimental studies indicate a potential cancer prevention effect for statins. Given the increasing prevalence of statin use, and the increasing incidence of hepatocellular carcinoma (HCC), the potential association between statins and HCC is an important issue to examine. METHODS: We conducted a matched case-control study nested within a cohort of patients with diabetes. Cases comprised incident HCC at least 6 months after entry in the cohort. Controls were identified by incidence density sampling from patients who remained at risk at the date of the HCC diagnosis matched by age and sex. We identified filled statin prescriptions as well as several potential confounding conditions, medications, as well as propensity score to use statins. Odds ratios (ORs) as estimates of the relative risk for HCC associated with statin use and 95% confidence intervals were obtained using conditional logistic regression. RESULTS: We examined 1303 cases and 5212 controls. The mean age was 72 years and 99% were men. A significantly smaller proportion of cases (34.3%) had at least one filled prescription for statins than controls (53.1%). There were no significant associations between HCC and nonstatin cholesterol- or triglyceride-lowering medications. The unadjusted OR for any statin prescription was 0.46 (95% confidence interval, 0.40-0.517) and the adjusted OR was 0.74 (95% confidence interval, 0.64-0.87). To reduce the potential confounding effect of existing liver disease, we ran the analyses in a subgroup of patients without recorded liver disease; the ORs were slightly attenuated but remained highly significant for any statin prescription (0.63; 95% confidence interval, 0.50-0.78). CONCLUSIONS: Statin use is associated with a significant reduction in the risk of HCC among patients with diabetes.
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Case-control studies have shown that statin intake is associated with a reduced risk of MASLD, MASH and liver fibrosis, as well as a reduction in the risk of hepatic decompensation, mortality and HCC in individuals with cirrhosis.
“Casecontrol studies have shown that statin intake is associated with a reduced risk of MASLD, MASH and liver fi brosis, 393 as well as a reduction in the risk of hepatic decompensation, mortality and HCC in individuals with cirrhosis.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [394]
Citation 393 follows the claim about reduced risk of MASLD, MASH and liver fibrosis. The Results and Discussion report a case-control association between statin prescriptions and reduced HCC risk, but do not report reduced risk of those three conditions. The Discussion mentions NAFLD among HCC cases and a possible effect on collagen-producing cells, neither of which establishes the cited claim. (LLM, conf=0.76)
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- Authors
- El–Serag, H. B., Johnson, M. L., Hachem, C., & Morgana, R. O.
- Affiliations
- University of Houston (US)
- Michael E. DeBakey VA Medical Center (US)
- ORCID
- Johnson, Michael L.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 136
- Issue
- 5
- Pages
- 1601-1608
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2677134
- OpenAlex
- W2018593069
- Cited by
- 291
- References
- 27
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 12 · 2023: 7 · 2022: 11 · 2021: 14 · 2020: 17 · 2019: 12 · 2018: 14 · 2017: 19 · 2016: 19 · 2015: 23 · 2014: 23 · 2013: 29 · 2012: 29
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Gastroenterology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American College of Gastroenterology
- National Institutes of Health (K24DK078154-03)
- U.S. Department of Veterans Affairs
- Health Services Research and Development (IIR 02-081)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- statins, hepatocellular carcinoma, diabetes mellitus, cancer prevention, statin use, liver disease, cholesterol-lowering drugs, drug-induced cancer risk
- MeSH terms
- Aged, Female, Carcinoma, Hepatocellular, Humans, Liver Diseases, Liver Neoplasms, Male, Risk, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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