Novel eicosanoid signature in plasma provides diagnostic for metabolic dysfunction-associated steatotic liver disease

Abstract

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301). Samples of control subjects were obtained from cohort studies at the University of California San Diego (control group; N = 48). Plasma samples were utilized for targeted quantitation of circulating eicosanoids, related bioactive metabolites, and polyunsaturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) lipidomics analysis. Bioinformatic approaches were used to discover a panel of bioactive lipids that can be used as a diagnostic tool to identify MASLD. The final panel of fifteen lipid metabolites consists of 12 eicosanoid metabolites and 3 free fatty acids that were identified to be predictive for MASLD by multivariate area under the receiver operating characteristics curve (AUROC) analysis. The panel was highly predictive for MASLD with an AUROC of 0.999 (95% CI = 0.986–1.0) with only one control misclassified. A validation study confirmed the resulting MASLD LIPIDOMICS SCORE, which may require a larger-scale prospective study to optimize. This predictive model should guide the development of a non-invasive “point-of-care” test to identify MASLD patients requiring further evaluation for the presence of metabolic dysfunction-associated steatohepatitis.