Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis.


Journal

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN: 1424-3911
Titre abrégé: Pancreatology
Pays: Switzerland
ID NLM: 100966936

Informations de publication

Date de publication:
Oct 2020
Historique:
received: 29 07 2020
revised: 26 08 2020
accepted: 30 08 2020
pubmed: 25 9 2020
medline: 18 9 2021
entrez: 24 9 2020
Statut: ppublish

Résumé

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. To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. 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. 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). 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP.
METHODS 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 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 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.

Identifiants

pubmed: 32967795
pii: S1424-3903(20)30674-8
doi: 10.1016/j.pan.2020.08.025
pii:
doi:

Substances chimiques

Biomarkers 0
Trypsinogen 9002-08-8

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1368-1378

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest DCW serves as a consultant to AbbVie, Regeneron and Ariel Precision Medicine and may have financial interest in Ariel Precision Medicine, MAA served as a consultant to GSK and Boehringer-Ingelheim. MDB serves as a consultant to Ariel Precision Medicine and NovoNordisk.

Auteurs

Wei Zhan (W)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Venkata Akshintala (V)

Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Phil J Greer (PJ)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Julia B Greer (JB)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Samer Alkaade (S)

Department of Medicine, Saint Louis University, St. Louis, MO, USA.

Michelle A Anderson (MA)

Department of Medicine, University of Michigan, Ann Arbor, MI, USA.

Thiruvengadam Muniraj (T)

Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.

Georgios I Papachristou (GI)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Bimaljit S Sandhu (BS)

Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.

Adam Slivka (A)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

C Mel Wilcox (CM)

Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA.

Melena D Bellin (MD)

Department of Pediatrics, University of Minnesota Medical Center and Masonic Children's Hospital, Minneapolis, MN, USA.

Vikesh K Singh (VK)

Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Dhiraj Yadav (D)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Randall E Brand (RE)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

David C Whitcomb (DC)

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: whitcomb@pitt.edu.

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Classifications MeSH