Prospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2024; 30(19): 2538-2552
Published online May 21, 2024. doi: 10.3748/wjg.v30.i19.2538
Non-pancreatic hyperlipasemia: A puzzling clinical entity
Krisztina Eszter Feher, David Tornai, Zsuzsanna Vitalis, Laszlo Davida, Nora Sipeki, Maria Papp
Krisztina Eszter Feher, David Tornai, Zsuzsanna Vitalis, Laszlo Davida, Nora Sipeki, Maria Papp, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hajdu-Bihar, Hungary
Krisztina Eszter Feher, Kalman Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
Author contributions: Feher KE, Papp M and Vitalis Z made the concept and designed the present study; Feher KE and Davida L were responsible for clinical data acquisition; Tornai D and Sipeki N made the laboratory measurement and were responsible for laboratory data acquisition; Tornai D, Feher KE, Sipeki N, Papp M made the analysis and interpretation of the data, and wrote paper; Papp M and Vitalis Z and Davida L supervised the work, provided expert insights and made critical revisions related to important intellectual content of the manuscript; All authors have read and approved the final manuscript.
Supported by the Economic Development and Innovation Operative Program Grant, No. GINOP 2.3.2- 15-2016-00048 “StayAlive”; and Human Resources Development Operational Program Grant of the National Research Development and Innovation Office, No. EFOP-3.6.2-16-2017-00006.
Institutional review board statement: The study was reviewed and approved by the Committee of Science and Research Ethics of the Hungarian Medical Research Council (ETT TUKEB) and the Regional and Institutional Committee of Science and research Ethics of the University of Debrecen (RKEB) (305/2014, 30595-1/2014 EKU, 55961-2/2016/EKU, 5753-2/2018 EKU).
Clinical trial registration statement: Our manuscript is an observational study based on a prospective data collection driven from the screening process of the Early Achievable Severit Y (EASY) trial (Registration number: ISRCTN10525246). However, patients with non-pancreatic hyperlipasemia who are the focus of our present study, were screened but not enrolled to the trial. Furthermore, all patients included in the current study are exclusively recruited from our clinic, while the trial was a multi centre investigation.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Patients' clinical data cannot be made public according to Hungarian law, but anonymized data can be obtained from the corresponding author on reasonable request at papp.maria@med.unideb.hu.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria Papp, DSc, FEBG, MD, PhD, Professor, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei Blv 98, Debrecen H-4032, Hajdu-Bihar, Hungary. papp.maria@med.unideb.hu
Received: January 1, 2024
Revised: March 7, 2024
Accepted: April 23, 2024
Published online: May 21, 2024
Processing time: 139 Days and 9.3 Hours
Abstract
BACKGROUND

Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.

AIM

To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.

METHODS

A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.

RESULTS

A total of 808 patients [male, n = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% vs 5.1%, P < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, P < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.

CONCLUSION

NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.

Keywords: Non-pancreatic hyperlipasemia; Acute pancreatitis; Glycoprotein 2; Acute kidney injury; Sepsis; Mortality

Core Tip: Non-pancreatic hyperlipasemia is a common and puzzling clinical entity in the differential diagnosis of acute pancreatitis (AP). The etiology of NPHL varies; however, sepsis and acute kidney injury (AKI) are the most prevalent causes. NPHL was associated with a high in-hospital mortality rate (22.4%). A readily available laboratory marker, the neutrophil-to-lymphocyte ratio, with a cut-off value > 10.37, has been the best independent laboratory predictor of mortality, with a nearly 4-fold increased risk. In the laboratory diagnosis of AP, the presence of complications, especially sepsis and AKI, warrants clinical attention, as it has a significant negative impact on the diagnostic accuracy of lipase.