Metabolites and lipoproteins may predict the severity of early Acute Pancreatitis in a South African cohort

Background: Acute pancreatitis (AP) is a common clinical disease with varying severity. The Revised Atlanta Classification (RAC) categorises AP into mild, moderately severe, and severe (MAP, MSAP and SAP) respectively. Despite the availability of different scoring systems to triage patients, these are not always suitable for predicting the course and outcome of certain patients during admission. In this study, untargeted metabolomics was used to identify metabolic parameters that can potentially be used as prognostic markers for stratifying the risk profile of patients for improved management and treatment. Methods: Serum isolated from blood samples collected from 30 AP patients (8 MAP, 14 MSAP, and 8 SAP) and 9 healthy control (HC) individuals was analysed using 1H nuclear magnetic resonance (NMR) spectroscopy. Wilcoxon and Kruskal Wallis rank-sum tests were used to compare differences in numerical covariates. A liposcale test was used for lipoprotein characterisation and the Spearman rank test was conducted for correlation of the data. P-values < 0.05 were considered significant. Results: Elevated levels of lactate, (rho = 0.67; p-value < 0.001, FDR = 0.001), 3-hydroxybutyrate (rho = 0.46; p-value < 0.003, FDR = 0.013), acetoacetate (rho = 0.63; p-value < 0.001, FDR < 0.001) and lipid alpha-CH2 (rho = 0.45; p-value = 0.004, FDR = 0.013) were associated with AP severity as was decreased levels of ascorbate (rho = 0.46; p-value < 0.003, FDR = 0.013), methanol (rho = 0.46; p-value < 0.003, FDR = 0.013), glutamine (rho = -0.55; p-value < 0.001, FDR = 0.002), ethanol (rho = 0.64; p-value < 0.001, FDR< 0.001), protein-NH (rho= -0.75; p-value < 0.001, FDR<0.001) among others. HDL-C decreased while IDL-C and VLDL-C increased across all the AP metabolic phenotypes compared to the HC. Conclusion: Dysregulated metabolites and lipids can potentially add to the understanding of the pathophysiological conditions of AP and can aid in the early prognosis and stratification of patients for specialist care. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the South African National Research Foundation Grant 121277 and the University of the Witwatersrand Faculty Research Committee Individual Grant 001254844110151211055254. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics clearance for this study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand (Ethics No. M190407). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors