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Lookup NU author(s): Professor Helen ReevesORCiD, Misti McCainORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2022 Authors. Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC. Methods: We assessed the profile of 273 lipid and small molecule metabolites by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry in serum from patients with MAFLD (n = 113) and MAFLD-associated HCC (n = 144) from six different centers. Regression models were used to identify a predictive model of HCC. Results: Twenty lipid species and one metabolite, reflecting changes in mitochondrial function and sphingolipid metabolism, were associated with the presence of cancer on a background of MAFLD with high accuracy (AUC 0.789, 95% CI: 0.721-0.858), which was enhanced with the addition of cirrhosis to the model (AUC 0.855, 95% CI: 0.793-0.917). In particular, the presence of these metabolites was associated with cirrhosis in the MAFLD subgroup (p < 0.001). When considering the HCC cohort alone, the metabolic signature was an independent predictor of overall survival (HR 1.42, 95% CI: 1.09-1.83, p < 0.01). Conclusion: These exploratory findings reveal a metabolic signature in serum which is capable of accurately detecting the presence of HCC on a background of MAFLD. This unique serum signature will be taken forward for further investigation of diagnostic performance as biomarker of early stage HCC in patients with MAFLD in the future.
Author(s): Lu H, George J, Eslam M, Villanueva A, Bolondi L, Reeves HL, McCain M, Chambers E, Ward C, Sartika D, Sands C, Maslen L, Lewis MR, Ramaswami R, Sharma R
Publication type: Article
Publication status: Published
Journal: Liver Cancer
Year: 2023
Volume: 12
Issue: 1
Pages: 19-31
Print publication date: 01/02/2023
Online publication date: 08/07/2022
Acceptance date: 25/06/2022
Date deposited: 14/03/2023
ISSN (print): 2235-1795
ISSN (electronic): 1664-5553
Publisher: S. Karger AG
URL: https://doi.org/10.1159/000525911
DOI: 10.1159/000525911
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