NEW DISCOVERIES IN THE ASSOCIATIONS OF STATIN MEDICATION EXPOSURE AND LIVER CIRRHOSIS-RELATED SEQUELAE

Abstract

Abstract

Background Statin association with decreased hepatocellular carcinoma (HCC) in subjects with liver cirrhosis and diabetes mellitus type 2 (DM2) has been sparsely studied. Numerous other observational studies and meta-analyses have demonstrated an association with statin exposure and delayed onset of HCC in subjects with liver cirrhosis alone.

Methods In this retrospective observational cohort study, we selected 423 subjects with liver cirrhosis and DM2 from the Massachusetts General Brigham health care system from 1 January 2004 to 25 July 2022. Data on statin usage, date of death, date of HCC, and confounders known to increase the risk of HCC were collected. Survival analysis was conducted for time to event to first HCC. We determined the hazard ratio for the association using Cox Proportional Hazards Regression Model. Additional sensitivity analyses were conducted with Cox regression with Propensity Score (PS) as a continuous variable or as a categorical variable (decile groups).

Results The total follow-up period was 9.2 years. The Kaplan-Meier Curve showed that the there was a divergence between statin-unexposed and statin exposed groups (p-value = .01) when treating statin exposure as time-fixed. Cox regression with time-varying treatment showed a HR of 0.43 favoring statin exposure (95%CI: 0.15–0.77). Cox regression utilizing PS as a categorical variable in the regression model in deciles resulted in a HR of 0.44 (95%CI: 0.20 – 0.95), and Cox regression utilizing PS as a continuous variable in the regression model resulted in a HR of 43 (p-value = 0.01, 95% CI 0.19 – 0.92) also favoring statin exposure.

Conclusion Our results show a strong association between statin exposure and delayed onset of HCC in our subject population across multiple analyses. Further observational or prospective studies are needed to confirm or refute these findings.