Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis

• Published in: Frontiers in endocrinology (Lausanne) Vol. 13; p. 896334
• Main Authors: Chang, Jae Seung, Ahn, Jhii-Hyun, Kang, Seong Hee, Koh, Sang-Baek, Kim, Jang-Young, Baik, Soon Koo, Huh, Ji Hye, Lee, Samuel S., Kim, Moon Young, Park, Kyu-Sang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.05.2022
• Subjects: adiponectin-to-leptin ratio; Biomarkers; central obesity; Endocrinology; FGF19; FGF21; Humans; mitochondria; Mitochondria - pathology; non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - pathology; Stress, Physiological; biopsy-proven fatty liver; non-alcoholic fatty liver disease; FGF19; adiponectin-to-leptin ratio; mitochondria; MRI-PDFF; central obesity; FGF21
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2022.896334

Mitochondrial dysfunction with oxidative stress contributes to nonalcoholic fatty liver disease (NAFLD) progression. We investigated the steatosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers. Altogether, 343 subjects who underwent magnetic resonance imaging-based liver examinations from a population-based general cohort, and 41 patients enrolled in a biopsy-evaluated NAFLD cohort, participated in the development and validation groups, respectively. Serologic stress biomarkers were quantitated by enzyme-linked immunosorbent assay. Multivariate regression showed that waist-to-hip ratio, fibroblast growth factor (FGF) 21, FGF19, adiponectin-to-leptin ratio, insulin, albumin, triglyceride, total-cholesterol, and alanine-aminotransferase were independent predictors of steatosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95%CI)] of the metabolic stress index for steatosis (MSI-S) was 0.886 (0.85-0.92) and 0.825 (0.69-0.96) in development and validation groups, respectively. MSI-S had higher diagnostic accuracy (78.1%-81.1%) than other steatosis indices. MSI-S notably differentiated steatosis severities, while other indices showed less discrimination. MSI-S, as a novel non-invasive index, based on mitochondrial stress biomarker FGF21 effectively predicted steatosis. Furthermore, MSI-S may increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.