Patients With Pancreatitis-Related Gene Variants Showed Higher Incidence of Hyperpancreatic Enzymemia After Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND

Post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) is the most severe adverse event associated with ERCP. Although numerous studies have identified risk factors for PEP, the role of genetic background in its development remains unexplored. The present study investigated the association between pancreatitis-related gene variants (PRG-variants) and PEP.

METHODS

This prospective, single-center study included 94 patients with naïve papilla who underwent ERCP between October 2021 and August 2023. Targeted sequencing was performed to analyze variants in four PRGs: PRSS1, SPINK1, CTRC, and CPA1. Patients were classified into two groups based on the presence or absence of PRG-variants, and the incidences of PEP and of post-ERCP hyperpancreatic enzymemia (PEH) were compared.

RESULTS

PRG-variants, regardless of their pathogenicity, were identified in 16 (17%) patients. Among all cases, PEP occurred in four (4%) patients, and PEH occurred in 27 (29%) patients. The incidence of PEP did not differ significantly with and without PRG-variants (p = 0.532). However, the group with PRG-variants had a significantly higher incidence of PEH, as demonstrated by both univariate (p = 0.013) and multivariate analyses (odds ratio, 6.291; 95% confidence interval, 1.133-34.934).

CONCLUSIONS

The present pilot study suggests that patients with PRG-variants, regardless of their pathogenicity, demonstrated a significantly higher incidence of PEH but not PEP. PEH may reflect pancreatic parenchyma injury and may progress to PEP when additional factors are present. Thus, PRG-variants may contribute to biochemical pancreatic injury after ERCP. Further large-scale studies and comprehensive genomic profiling of patients with PEH/PEP are warranted.

TRIAL REGISTRATION: The central ethics committee approved the study protocol (M21-0066).