Does non-alcoholic fatty liver disease increase the risk for pancreatic cancer? A multi-center retrospective cohort study.

4165 Background: Recent studies suggest that patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of hepatic and extra-hepatic gastrointestinal cancers. However, there is limited data exploring the risk of pancreatic cancer (PC) in patients with NAFLD. We aim to investigate the risk of PC in patients with biopsy proven NAFLD. Methods: We performed a multicenter retrospective cohort study utilizing an electronic health record database (TriNetX) to study the risk of PC in patients with NAFLD. The study group comprised adults ≥40 years with NAFLD who had undergone liver biopsy between January 2016 to December 2019. Comparison group was obese individuals (body mass index ≥30 kg/m 2 ) without NAFLD. We excluded patients with other etiologies of chronic liver disease. The median follow up was 5 years. Patients who had follow up visits 1-4 years were selected. The primary outcome was a new diagnosis of PC. Results: We identified 18,513 patients with NAFLD and had undergone liver biopsy, predominantly white (75.3%) females (59.7%). Diabetes mellitus (29.4% vs. 18.8%), chronic pancreatitis (1.3% vs. 0.2%), pancreatic cyst (0.8% vs. 0.2%), tobacco use (9.4% vs. 7.7%), and a family history of GI cancers (2.7% vs. 1.5%) were observed more commonly in the NAFLD group compared with the obese control. After propensity score matching for confounding variables, the 5-year risk of developing PC was higher in NAFLD cohort (risk ratio, RR 2.18, 95% CI 1.56-3.03) compared with the control group. Overall, 5-year mortality was higher in the NAFLD cohort (8.2% vs 6.6%, RR 1.25, 95% CI 1.16-1.37). Conclusions: NAFLD probably increases the risk of pancreatic cancer in middle-aged and elderly individuals and the risk exists despite controlling for obesity and other known risk factors for PC. NAFLD should be considered in the risk stratification strategy for pancreatic cancer. Moreover, patients with NAFLD and advanced fibrosis who undergo screening for hepatoma may be considered for abdominal CT or MRI for pancreatic cancer screening if other risk factors exist. [Table: see text]