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Introduction Serum Gamma-Glutamyl Transferase (GGT) is a reliable marker of oxidative stress and hepatobiliary dysfunction. However, its specific prognostic value for pancreatic pathology remains unknown. We aimed to evaluate the association between elevated serum GGT and the risk of developing pancreatic cysts in a large, multi-centre US cohort using the TriNetX US Collaborative NetworkMethods In this retrospective cohort study, adult patients were stratified by sex and serum GGT levels: high GGT (males >57 U/L; females >26 U/L) and low GGT (males <23 U/L; females <14 U/L). Patients with a history of pancreatic disease (acute/chronic pancreatitis, cysts, neoplasms) within 1 year of the index event were excluded. Propensity score matching was done to balance cohorts for age, race/ethnicity, BMI, and key comorbidities (hypertension, diabetes, CKD, alcohol use, smoking). The primary outcome comprised the 3-year risk of pancreatic cyst, while secondary outcomes included all-cause mortality and inpatient hospitalisation. Hazard Ratios (HR) with 95% Confidence Intervals (CI) were calculated using Cox proportional hazards models.Results After matching, there were 41484 patients (25130 males; 16354 females). In the male cohort (n=12565/group), high GGT was strongly associated with incident pancreatic cysts (0.4% vs 0.2%; HR 1.92; p=0.004), along with higher all-cause mortality (14.8% vs 5.8%; HR 2.67; p<0.001) and hospitalisation (31.6% vs 22.3%; HR 1.55; p<0.001). In the female cohort (n=8177/group), high GGT was associated with incident pancreatic cysts (0.4% vs 0.2%; HR 1.96; p=0.018), higher all-cause mortality (8.6% vs 2.6%; HR 3.37; p<0.001) and hospitalisation (27.8% vs 19.0%; RR 1.47; p<0.001).Conclusion Persistently elevated serum GGT is associated with approximately two-fold increased hazard of pancreatic cyst development in both sexes. High GGT also identifies those at significantly higher risk of all-cause mortality and hospitalisation across both sexes, suggesting that GGT may serve as a valuable, low-cost biomarker for risk stratification in pancreatic surveillance.Abstract P151 Table 1Risk of outcomes at 3 years (matched cohorts)OutcomeHigh GGT (n, Risk)Low GGT (n, Risk)Hazard Ratio (95% CI)P-ValueFEMALES (n=16354)Pancreatic Cyst35 (0.4%)18 (0.2%)1.96 (1.11–3.46)0.018All-Cause Mortality707 (8.6%)212 (2.6%)3.37 (2.89–3.93)<0.001Hospitalisation2273 (27.8%)1551 (19.0%) 1.47 (1.39–1.55)<0.001MALES (n=25130)Pancreatic Cyst53 (0.4%)29 (0.2%)1.92 (1.22–3.03)0.004All-Cause Mortality1862 (14.8%)734 (5.8%)2.67 (2.45–2.91)<0.001Hospitalisation3972 (31.6%)2799 (22.3%)1.55 (1.47–1.62)<0.001