Abstract
We aimed to examine whether statin users have a lower risk of hepatocellular carcinoma (HCC) after careful consideration of prevalent statin use and cholesterol levels. During a mean prospective follow-up of 8.4 years in 400,318 Koreans, 1686 individuals were diagnosed with HCC. When prevalent users were included, HCC risk was reduced by >50% in statin users, regardless of adjustment for total cholesterol (TC). When prevalent users were excluded, new users who initiated statins within 6 months after baseline had a 40% lower risk of HCC (hazard ratio [HR] = 0.59) in a TC-unadjusted analysis. However, this relationship disappeared (HR = 1.16, 95% CI = 0.80–1.69) after adjusting for TC levels measured within 6 months before statin initiation. TC levels had strong inverse associations with HCC in each model. High cholesterol levels at statin initiation, not statin use, were associated with reduced risk of HCC. Our study suggests no protective effect of statins against HCC.
Highlights
Over 20 observational studies have suggested that statins protect against hepatocellular carcinoma (HCC) development.[1,2,3,4,5] Most of those studies included individuals who had been using statins for some time before enrolment, the inclusion of prevalent users can introduce biases in observational studies of efficacy.[6]
After adjustment for baseline total cholesterol (TC) levels measured within 6 months before statin initiation, the protective effects of statins against HCC disappeared
A major bias related to prevalent users is the inability to control for confounders that may be altered by statins.[10]
Summary
Over 20 observational studies have suggested that statins protect against hepatocellular carcinoma (HCC) development.[1,2,3,4,5] Most of those studies included individuals who had been using statins for some time before enrolment, the inclusion of prevalent users can introduce biases in observational studies of efficacy.[6]. Our prospective cohort study aimed to examine whether statin use was associated with a reduced risk of HCC after careful consideration of cholesterol levels and exclusion of prevalent users
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