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Statins Tied to Lower HCC Risk in HBV Group Without Cirrhosis
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AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
A nationwide Korean case-control study linked aspirin and statin use to a lower risk of hepatocellular carcinoma (HCC) in antiviral-naive people with chronic HBV but without cirrhosis [1]. But further analysis cast doubt on the association of aspirin use with lower HCC risk, while the statin association with lower risk stayed strong.
Although aspirin and statins often get prescribed together, say University of Ulsan researchers who conducted this study, no work has assessed the combined impact of these antiinflammatory agents on HCC risk. The investigators suggested clinicians seem more likely to prescribe aspirin and statins for people with treated HBV but without cirrhosis, who have a lower HCC risk, than for people with cirrhosis, whose HCC risk runs higher.
To get a better understanding of the individual and combined impact of aspirin and statins on HCC development, a Korean team conducted a nationwide case-control study and then comparisons within historical cohorts. Study groups came from more than 834,000 people with data in the Korean National Health Insurance Service between 2005 and 2015.
For the case-control study the researchers defined cases as people admitted to the hospital with a first diagnosis of HCC. Randomly selected controls were people without HCC matched to cases in a 1-to-4 ratio for age, sex, cohort entry year, follow-up duration, and biennial general health exam status. The index date was the first diagnosis of chronic HBV infection according to ICD-10 code. To explore associations between aspirin and statins and HCC risk, the researchers used conditional logistic regression adjusted for age, sex, socioeconomic status, diabetes, hypertension, and concomitant medications.
To create historical cohorts, the researchers excluded people who took aspirin or a statin in the 2 years before the index date and used aspirin and statins irregularly during the period of the case-control study. The final aspirin historical cohort had 673,107 people and the statin historical cohort had 588,045. Follow-up ran from the index date to HCC diagnosis, death, liver transplant, antiviral therapy, or December 31, 2017.
The matched case-control analysis had 15,645 cases and 62,580 controls, 76% of them men, with ages averaging 53.7 years (cases) and 53.4 years (controls). About one quarter of cases and controls had diabetes, and about 44% had hypertension. Proportions of cases and controls taking aspirin were 19% and 24% and taking a statin 15% and 29%.
Compared with people who never used aspirin, those who ever used it had about 10% lower odds of HCC (adjusted odds ratio [aOR] 0.89, 95% confidence interval [CI] 0.85 to 0.94). The statin impact was greater: Compared with never-users, people who ever used statins had a 60% lower chance of HCC (aOR 0.39, 95% CI 0.36 to 0.40).
Compared with people who never used aspirin or a statin, HCC odds proved lower for those who used aspirin but not a statin (aOR 0.87, 95% CI 0.82 to 0.93) and lower still for those who used a statin but not aspirin (aOR 0.37, 95% CI 0.35 to 0.40). The odds ratio for this statin-only group was similar to the group that used both aspirin and a statin (aOR 0.34, 95% CI 0.32 to 0.37). Compared with no statin use, each higher cumulative statin dose further lowered odds of HCC. But taking more aspirin did not drive-down HCC risk in a dose-dependent manner.
The aspirin historical cohort had 59,672 cases and the same number of propensity score-matched controls. The statin historical cohort had 46,870 cases and the same number of propensity score-matched controls. In an unadjusted analysis of the aspirin historical cohort, aspirin-treated people had a higher risk of HCC than aspirin-untreated people (hazard ratio [HR] 1.16, 95% CI 1.09 to 1.23, P < 0.001). In a multivariable adjusted model, aspirin-treated people ran a lower HCC risk than aspirin-untreated people (HR 0.67, 95% CI 0.63 to 0.72, P < 0.001). In the unadjusted analysis of the statin historical cohort, statin takers had a 50% lower risk of HCC than statin-untreated people (HR 0.50, 95% CI 0.45 to 0.55, P < 0.001). In a multivariable adjusted model, statin-treated people had a two-thirds lower HCC risk than statin-untreated people (HR 0.33, 95% CI 0.30 to 0.27, P < 0.001).
Further analysis of the aspirin historical cohort determined that aspirin-untreated people treated with a statin (versus statin-untreated) had an HCC risk reduction similar to aspirin-treated people treated with a statin (versus statin-untreated): HRs 0.31 and 0.38 (P < 0.001 for both comparisons). In contrast, analysis of the statin historical cohort determined that statin-untreated people treated with aspirin (versus aspirin-untreated) and statin-treated people also treated with aspirin (versus aspirin-untreated) did not have a lower HCC risk: HRs 1.00 (P = 0.97) and 0.98 (P = 0.84). These results suggest that statins drive the HCC risk reduction with aspirin, but aspirin prophylaxis has no impact on HCC risk reduction with a statin.
The researchers concluded that statins, but not aspirin, "showed consistent and significant dose-dependent reductions in risk of HCC regardless of study design." Because aspirin was not associated with lower HCC risk in stratified analyses, it appears that "the benefit of aspirin may have been confounded by statin use."
Reference
1. Choi WM, Kim HJ, Ko MJ, et al. Association of aspirin and statin use with hepatocellular carcinoma risk in treatment-naïve non-cirrhotic patients with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 137.
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