Aspirin for Primary Prevention in Metabolic Dysfunction-Associated Steatotic Liver Disease.

We read with great interest the recent study by Tsutsumi et al. in Hepatology Research, which reports an association between aspirin use for primary prevention and increased all-cause mortality in individuals aged 65 and older with metabolic dysfunction-associated steatotic liver disease (MASLD) and no known cardiovascular disease (CVD) [1]. We concur that this estimate (HR: 9.82), which is based on a limited number of events and has a very wide confidence interval (95% CI: 1.15–83.69), warrants a cautious interpretation. Nonetheless, this finding contributes to the ongoing discussion about the risk-benefit profile of aspirin in vulnerable patient populations. Notably, the authors also reported a significant aspirin-by-diet interaction, suggesting that higher adherence to a Mediterranean diet may mitigate this associated risk [1]. The observation by Tsutsumi et al. adds to a growing body of evidence questioning the role of aspirin in primary prevention. The challenge of inappropriate aspirin use in clinical practice is well-documented. This concern is underscored by real-world data from the ASSOS study, which found that 71% of patients prescribed aspirin for primary prevention in Turkish cardiology outpatient clinics were using it in a manner inconsistent with guideline recommendations [2]. This finding suggests that the potential risks highlighted by Tsutsumi et al. in the MASLD population may be relevant to a broader pattern of use in clinical practice. Current international guidelines have also shifted away from broadly recommending aspirin for primary prevention. The 2021 European Society of Cardiology (ESC) Guidelines on CVD prevention, informed by major trials such as ASPREE, ARRIVE, and ASCEND, do not recommend routine aspirin for this purpose due to an unfavorable benefit-risk balance, particularly noting an increased risk of major bleeding in older adults without established CVD [3]. In conclusion, the study by Tsutsumi et al. is a significant alarm, revealing the potential harms of using aspirin for primary prevention in older adults with chronic liver conditions such as MASLD. When combined with the widespread inappropriate use shown by the ASSOS study and the clear recommendations from the ESC guidelines, it is imperative that clinicians embrace the principle of “primum non nocere” (first, do no harm). Before prescribing aspirin, especially in such sensitive patient groups, healthcare providers should carefully evaluate the risk-benefit balance. Although acknowledging the inherent limitations of observational data, including the potential for residual confounding and limited granularity of drug exposure, this work underscores the importance of a careful individualized risk-benefit assessment before prescribing aspirin, especially in older patient groups with comorbidities. The authors declared that this study had received no financial support. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.