P1 The chemoprotective effect of anti-platelet agents on obesity-related cancer incidence in people with metabolic dysfunction associated steatotic liver disease

<h3>Introduction</h3> Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest growing cause of chronic liver disease and is a multisystem disease associated with increased risk of extrahepatic cancer in addition to hepatocellular carcinoma (HCC). In people with chronic liver disease, aspirin may confer protection against HCC. To our knowledge the chemoprotective benefits of aspirin and other anti-platelet agents have not been explored in people with MASLD for other obesity-related cancers. Using a large international cohort of patients, we explored the impact of aspirin, and other anti-platelet agents, for the prevention of all obesity-related cancers including HCC, in people with MASLD. <h3>Methods</h3> We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (Cambridge, MA, USA), a global federated database. We identified adults aged 18 or over with a diagnosis of MASLD, prior to commencing antiplatelet agents. Two groups were created: antiplatelet versus no antiplatelet use. We propensity score matched for nine variables. Antiplatelet use was defined as aspirin, ticagrelor, cangrelor, clopidogrel or prasugrel use for at least one year. Follow up was for 5 years. We performed a subgroup analysis on aspirin users only, and stratified by sex, age, and length of exposure. <h3>Results</h3> Antiplatelet use in people with MASLD was associated with statistically significant reduction in all obesity-related cancers (HR 0.75, 95% CI 0.68–0.83, p&lt;0.001) and individually for hepatocellular carcinoma (HR 0.51, 95% CI 0.39–0.67, p&lt;0.001, figure 1), breast carcinoma (HR 0.75, 95% CI 0.63–0.88, p=0.001), pancreatic carcinoma (HR 0.70, 95% CI 0.54–0.92, p=0.010) and colorectal carcinoma (HR 0.71, 95% CI 0.58–0.88, p=0.002). For women, there was a significant reduction in risk of ovarian carcinoma (HR 0.67, 95% CI 0.47–0.95, p=0.024). There was no significant difference between users and non-users of anti-platelet agents in incidence of gallbladder carcinoma, gastric carcinoma, oesophageal carcinoma, uterine carcinoma, multiple myeloma and thyroid carcinoma. Aspirin monotherapy was similarly associated with reduced incidence of all obesity-related cancers (HR 0.75, 95% CI, 0.67–0.85, p&lt;0.001), with benefits observed in males (HR 0.56, 95% CI 0.45–0.71, p&lt;0.001), females (HR 0.78, 95% CI 0.68–0.90, p=0.001) and in older and younger people (HR 0.71, 95% CI 0.63–0.81, p&lt;0.001; HR 0.68, 95% CI 0.52–0.89, p=0.005). <h3>Conclusion</h3> Our study highlights the novel potential of anti-platelet therapy, notably aspirin, in reducing the incidence of several hepatic and extra-hepatic obesity-related cancers, in individuals with MASLD, a high-risk population. Randomised, controlled studies should explore their potential primary cancer prevention role.