Statin use and liver-related prognosis among patients with MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver condition. We investigated whether statin use reduces liver-related events (LREs) risk among patients with MASLD or MASLD with increased alcohol intake (MetALD). This nationwide cohort study included individuals aged ≥40 years with MASLD/MetALD undergoing health examinations between 2012 and 2013. The primary outcome was LREs; hepatocellular carcinoma (HCC), decompensated liver cirrhosis (DLC), and liver-related mortality. Secondary outcomes included HCC, DLC, and steatotic liver disease (SLD) regression, all-cause mortality, cardiovascular diseases (CVD)-related mortality, and liver-related mortality, respectively. Multivariable Cox regression was performed to estimate the risk of LREs associated with statin use. Among 516,575 individuals (median follow-up: 10.1 years), statin users experienced significantly lower LRE rates (1.6%) compared with non-users (2.0%, p <0.001). Multivariable Cox regression analysis revealed that statin use was associated with reduced risks of LREs (adjusted hazard ratio [aHR] 0.64, 95% CI 0.61-0.68), HCC (aHR 0.52, 95% CI 0.47-0.58), DLC (aHR 0.58, 95% CI 0.52-0.65), all-cause mortality (aHR 0.81, 95% CI 0.78-0.84), CVD-related mortality (aHR 0.87, 95% CI 0.80-0.95), and liver-related mortality (aHR 0.51, 95% CI 0.46-0.57). Furthermore, statin use was associated with SLD regression (aHR 1.18, 95% CI 1.15-1.21). Stratified analyses consistently demonstrated risk reductions across all subgroups, particularly in patients with elevated alanine aminotransferase levels. Sensitivity analyses confirmed the robustness of these associations. Statins are significantly associated with reduced LRE risk in patients with MASLD, especially among those with elevated alanine aminotransferase levels, suggesting a viable preventive strategy for such population. Our study provides critical evidence supporting the role of statins in reducing liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), a condition with significant global health impact. These findings are particularly relevant for clinicians managing high-risk patients with MASLD, especially those with elevated alanine aminotransferase levels, as they highlight the potential for statins to mitigate both liver and cardiovascular risks. By demonstrating the robustness of these results through comprehensive sensitivity and stratified analyses, our research underscores the importance of integrating statin therapy into the management of MASLD. This has practical implications for physicians, researchers, and policymakers in developing guidelines and preventive strategies to improve long-term liver and cardiovascular outcomes.