Metabolic Dysfunction-Associated Steatotic Liver Disease and Pancreatic Disease-A Population-Based Nationwide Cohort and Sibling-Controlled Study.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to pancreatic diseases, but evidence from population-based studies with liver histology is lacking.

Aims and methods: In this population-based cohort including all Swedish adults (n = 8563) with biopsy-proven MASLD, we aimed to investigate incidences of pancreatic diseases compared with matched reference individuals from the general population (n = 38,858) and full siblings (n = 6696). Using Cox proportional hazard models, we calculated multivariable adjusted hazard ratios (aHRs) and confidence intervals (CIs).

Results: We documented 359 incidents of pancreatic diseases in MASLD patients and 880 events in matched reference individuals, resulting in an incidence rate difference of 1.54 (95% CI, 1.25-1.84). The relative risk of pancreatic disease was highest in the first two years after MASLD diagnosis (aHR, 2.19 [95% CI, 1.92-2.50), but remained statistically significant increased even up to ten years [aHR, 1.60 (95% CI, 1.38-1.85)]. The most common pancreatic disease in individuals with MASLD was acute non-biliary pancreatitis (1.44 vs. 0.44 events/1000 PY), followed by chronic pancreatitis (0.54 vs. 0.12/1000 PY) and pancreatic cancer (0.88 vs. 0.47/1000 PY). We documented 130 versus 344 pancreas-related deaths among individuals with MASLD and their matched comparators, yielding an absolute risk difference of 0.51/1000 PY and an aHR of 2.41 (95%CI = 1.95-2.97). The findings were consistent in sibling-controlled analyses with an aHR of 2.21 (95%CI = 1.69-2.90).

Conclusions: MASLD was associated with significantly higher rates of acute and chronic pancreatitis of predominantly non-biliary origin, as well as an increased risk of pancreatic cancer and pancreas-related mortality.