Cystic Fibrosis Heterozygosity as a Risk Factor for Post-ERCP Pancreatitis: Implications for ERCP Risk Stratification...

Endoscopic retrograde cholangiopantography (ERCP) is widely utilized but carries a risk of post-ERCP pancreatitis (PEP), a major source of morbidity, mortality, and healthcare costs. Although known risk factors exist, the impact of cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator (CFTR)-related biology remains incompletely understood. CF affects ~ 30,000 individuals in the U.S. and often involves hepatobiliary disease requiring ERCP. To this end, we aim to determine whether CF heterozygosity carries an elevated risk of PEP following ERCP.

An analysis was conducted using patient data obtained from the Epic Cosmos cohort, a large-scale population health research platform developed by Epic Systems Corporation. Cosmos aggregates approximately 300 million patient records from participating centers. We included patients undergoing their first ERCP and who required at least one year of prior clinical observation. CF carrier status and CF diagnosis were ascertained using diagnostic codes. PEP was defined as a diagnosis of non-gallstone pancreatitis within 14 days post-ERCP. Multivariable logistic regression and entropy balancing were used for adjustment.

A retrospective analysis of 364,707 patients undergoing 593,660 ERCPs. Of these, 1,074 ERCPs were compared to controls. CF carrier patients were more likely to be female (65.9% vs. 53.9%), older, have prior ERCP (54.0% vs. 39.1%), receive rectal indomethacin (21.1% vs. 14.4%), but less likely to have cholangitis (9.9% vs. 19.6%). The unadjusted PEP rate was significantly higher in CF carriers (40.4% vs. 11.3%, OR = 5.33, p < 0.001). After adjustment, CF carrier status was associated with increased PEP risk (logistic regression: adjusted OR = 2.34, 95% CI: 2.03-2.69; entropy balancing: adjusted OR = 2.13, 95% CI: 1.83-2.48).

CF heterozygosity status is independently associated with a substantially increased risk of post-ERCP pancreatitis, suggesting that CFTR dysfunction may heighten pancreatic vulnerability during ERCP. Clinically, CF carriers may represent an underrecognized high-risk group who could benefit from more intensive pre-procedural risk assessment and optimized prophylactic strategies.