Introduction

Some data suggest a possible association between metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic disorders. However, evidence from population-based studies taking advantage of liver histology is lacking.

Aims & Methods

In this population-based cohort including all Swedish adults with biopsy-proven MASLD (1965-2017), we aimed to investigate the overall incidence of pancreatic diseases including acute and chronic pancreatitis, pancreatic cancer as well as pancreas-related mortality. Individuals with MASLD were matched to up to 5 individuals from the general population by age, sex, calendar year and county. Using the unique Swedish personal identity number, several validated nationwide registers were linked to obtain data on demographics, in- and outpatient diagnoses, prescribed medications, incident cancers, and causes of death. The primary endpoint of adverse pancreatic outcome was a composite of acute non-biliary pancreatitis, chronic pancreatitis, and pancreatic cancer. Secondary outcomes included each of the single outcomes as well as acute biliary pancreatitis and pancreas-related mortality. Using Cox proportional hazards modelling, we calculated multivariable adjusted HRs (aHRs). Sibling-controlled analyses were additionally performed to account for familial susceptibilities.

Results

In total, 8563 patients with biopsy-proven MASLD and 38,858 matched reference individuals were included.
Among MASLD patients, the average age at index biopsy was 54.5 years, and 56.9% were male.
Overall, we documented 359 incident adverse pancreatic outcomes in MASLD patients (2.74/1,000 person-years (PYs)) and 880 events in matched reference individuals (1.19/1000 PYs), resulting in one extra case of adverse pancreatic outcome in 65 MASLD patients followed-up for ten years (incidence rate difference: 1.54/1000 PYs).
After multivariable adjustment, the aHR for incident adverse pancreatic outcomes was 2.19 (95%CI=1.92-2.50).
Compared with reference individuals, the incidence rate differences and corresponding aHRs increased with worsening histologic MASLD severity with 2.46 /1,000 PYs (aHR, 2.07 [95%CI=1.77-2.43]) in simple steatosis, 3.39 /1,000 PYs (aHR, 2.69 [95%CI=1.83-3.96]) in non-fibrotic MASH, and 3.56 /1,000 PYs (aHR, 2.53 [95%CI=1.87-3.43]) in patients with MASLD-associated fibrosis or cirrhosis, respectively.
Compared to reference individuals, the most common adverse pancreatic outcome in individuals with biopsy-proven MASLD was acute non-biliary pancreatitis with 1.44 vs. 0.44/1,000 PYs, resulting in an aHR of 2.24 (95%CI=1.83-2.75).
Consistent with the results on acute pancreatitis, individuals with MASLD had significantly higher rates of developing chronic pancreatitis (0.54 vs. 0.12/1,000 PYs; aHR 3.78, 95% CI 2.70-5.29).
In addition, MASLD patients had significantly higher rates of incident pancreatic cancer (0.88 vs. 0.47 per 1000 PY), resulting in an absolute rate difference of 0.41/1,000 PYs.
We documented 130 vs. 344 pancreas-related deaths among individuals with MASLD and their matched comparators (0.97 vs. 0.46/1,000 PY), yielding an absolute risk difference of 0.51/1,000 PY and an aHR of 2.41 (95%CI=1.95−2.97).

Conclusion

In this nationwide histology cohort, MASLD was associated with significantly higher rates of acute non-biliary pancreatitis, chronic pancreatitis, and pancreatic cancer, all of which led to a higher risk of pancreas-related mortality. In contrast, the risk of biliary pancreatitis was only slightly increased. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

Disclosure

Disclosures: Dr Ludvigsson is coordinating a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from the Janssen corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national healthcare registers in China and has an ongoing collaboration about celiac disease with Takeda. Dr Vujasinovic and Dr Löhr have received lecture fees from Abbott and Viatris. Dr Ebrahimi has served on an advisory board for Boehringer Ingelheim. All other authors declare that they have no conflicts of interest and nothing to declare.
Grants and financial support: Swedish Magtarmfondens stipendium for research and Ruth and Richard Julin Foundation for research (Dr Vujasinovic). The Swedish Cancer Foundation (Dr Ludvigsson). Swiss National Science Foundation P500PM_210866 (Dr Ebrahimi).