Metabolite biomarker discovery for diagnosis of non-alcoholic fatty liver disease according to obesity status

Study Summary

We performed circulating lipidomic profiling of sera based on the histological severity of non-alcoholic fatty liver disease (NAFLD). Total 224 lipid metabolites were identified in sera from NAFLD patients, and the differences in circulating lipidomic profiles were compared according to NAFLD severity in the presence and absence of obesity as well as in whole populations. Marked alterations in glycerolipids, including diacylglycerol (DAG) and triacylglycerol (TAG) species, and saturated sphingomyelin (SM) species were observed in both the non-obese and obese groups, with an incremental increase from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH).

[Fig. 1] Alterations in fold changes of lipid species according to the obesity status and NAFLD severity

To predict the histological severity of NAFLD, a group of lipid metabolites that included DAGs, TAGs and SMs that were significantly different between NAFL and NASH patients were separately selected in non-obese and obese subjects using three-fold cross validation. Next, the areas under the receiver operator characteristic curve (AUROCs) were calculated using each combination of lipid metabolites to effectively discriminate subjects with NAFLD from subjects without NAFLD among all subjects and subjects with NASH from subjects with NAFL among NAFLD subjects. In the non-obese group, the AUROCs for NAFLD vs no-NAFLD and NASH vs NAFL were 0.916 and 0.813 respectively. The AUROCs were 0.967 and 0.812 for NAFLD vs noNAFLD and NASH vs NAFL in the obese group respectively.

[Fig. 2] The AUROCs for combinations of five and seven lipid metabolites to predict the histological severity of NAFLD in non-obese and obese groups

Our findings provide new insights that aid in the understanding of pathophysiological mechanisms responsible for the development and severity of non-obese NAFLD, which are relevant to precision medicine and personalised therapy based on various phenotypes of NAFLD. Moreover, lipid metabolite combinations are expected to be useful for the differential diagnosis of NAFLD from no-NAFLD and NASH from NAFL, regardless of the obesity status.