Abstract

The hepatoprotective effects of aspirin have been observed in individuals with viral hepatitis; however, its impact on the general population remains uncertain. Understanding the association between aspirin use and the development of liver diseases is crucial for optimizing preventive strategies. We identified individuals with aspirin use in the UK Biobank and the Penn Medicine Biobank, as well as propensity-score-matched controls. Outcome measures included new liver disease development, diagnosed by MRI or "International Classification of Diseases and Related Health Problems" coding, and incidences of gastrointestinal bleeding and ulcers. In the UK Biobank cohort, regular aspirin use was associated with an 11.2% reduction in the risk of developing new liver diseases during the average 11.84 ± 2.01-year follow-up period (HR=0.888, 95% CI = 0.819-0.963; p = 4.1 × 10-3). Notably, the risk of metabolic dysfunction-associated steatotic liver disease (ICD-10 K76.0) and MRI-diagnosed steatosis was significantly lower among aspirin users (HR = 0.882-0.911), whereas no increased risk of gastrointestinal bleeding or ulcers was observed. These findings were replicated in the Penn Medicine Biobank cohort, in which the protective effect of aspirin appeared to be dependent on the duration of intake. The greatest risk reduction for new liver disease development was observed after at least 1 year of aspirin use (HR = 0.569, 95% CI = 0.425-0.762; p = 1.6 × 10-4). Intriguingly, when considering general risk factors, only men exhibited a lower risk of MRI-confirmed or ICD-coded steatosis with aspirin use (HRs = 0.806-0.906), while no significant protective effect of aspirin was observed in females. This cohort study demonstrated that regular aspirin use was associated with a reduced risk of liver disease in men without an elevated risk of gastrointestinal bleeding or ulcers. Further investigation is warranted to elucidate potential sex-related differences in the effects of aspirin and to inform tailored preventive strategies for liver diseases.

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