Cholangitis alters iron-related parameters predominantly in cholangiocarcinoma: a prospective exploratory ERCP-based study

Pancreatobiliary tumor serum markers have limited diagnostic utility. Bile has emerged as a promising matrix for biomarker discovery. Acute cholangitis may interfere with biomarker interpretation. This study evaluated the impact of cholangitis on selected tumor biomarkers and on iron metabolism.

In this prospective study, 117 patients treated with endoscopic retrograde cholangiopancreatography (ERCP) were included, with the following indications for the procedure: choledocholithiasis (n=70), cholangiocarcinoma (CCA) (n=24), and pancreatic cancer (PC) (n=23). Bile samples were obtained during ERCP and analyzed using ECLIA (CA19-9, PIVKA-II, AFP, CEA, ferritin, CA125), colorimetric assays (iron, TIBC), and ELISA (hepcidin). Patients were stratified by diagnosis and by the presence of cholangitis.

Biliary infection did not significantly affect biliary CA19-9, CA125, or PIVKA-II across the analyzed disease groups. The most pronounced changes were observed in iron-related biomarkers, particularly in patients with CCA, who exhibited higher biliary iron, ferritin, and TIBC concentrations in the presence of concomitant cholangitis. Lower biliary hepcidin concentrations were observed only in patients with PC and concomitant cholangitis. However, these associations did not remain statistically significant after false discovery rate (FDR) adjustment.

Biliary infection appears to have a limited effect on conventional biliary tumor markers but may influence iron-related biomarkers, particularly in patients with CCA. Although these associations did not remain statistically significant after correction for multiple comparisons, they suggest that biliary iron metabolism may respond differently to cholangitis than conventional tumor markers. These findings should be considered hypothesis-generating and require validation in larger, multicenter cohorts.