Background: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. Aim: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. Methods: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. Results: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). Conclusions: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.
Bibliographical noteFunding Information:
This research was partly supported by the China Scholarship Council (WZ), NIH DK061451 (D.C.W.), DK077906 (D.Y.), U01 DK108306 (D.C.W. and D.Y.), and UL1TR000005 . The authors recognize the outstanding laboratory coordination and testing by Kimberly Stello, Danielle Dwyer and Nicole L. Komara. An abstract of the initial analysis was presented at the American Pancreatic Association annual meeting, November 2015.
- Pancreatic acinar cell
- Pancreatic beta cell
- Pancreatic stellate cell
- Pathologic calcification