Abstract

Background and Aims: Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. Methods: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). Results: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn’s disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. Conclusions: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.

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