Serum FGF21 as a predictor of hepatic steatosis severity in non-alcoholic fatty liver disease: an integrated molecular and clinical analysis.

Abstract

The aim of this paper is to assess serum fibroblast growth factor 21 (FGF21) concentration as a potential biomarker for hepatic steatosis severity in Non-Alcoholic Fatty Liver Disease (NAFLD) through an integrated molecular and clinical approach. This retrospective study assessed 120 NAFLD patients and collected clinical, biochemical, genomic, transcriptomic, and proteomic data. Integrated molecular analyses revealed that key lipid metabolism genes (PNPLA3, TM6SF2, GCKR) were significantly enriched in patients with severe steatosis, accompanied by upregulation of FGF21-related transcriptional pathways (PPARα and ATF4 signaling). Proteomic profiling demonstrated increased expression of lipid metabolism-associated proteins, while metabolomic analysis indicated elevated free fatty acids and disrupted ketone metabolism. These molecular alterations were strongly correlated with circulating FGF21 levels and hepatic fat fraction. Among all the tested parameters Serum FGF21 was identified as the most accurate predictor of severe hepatic steatosis with its concentration rising progressively from mild to severe conditions. The study also confirmed associations between metabolic disorders, markers of hepatic injury, and inflammation with disease progression. Multivariate logistic regression identified independent predictors, including BMI/obesity-related parameters, insulin resistance, indices of hepatic fibrosis, and alanine transaminase. Receiver operating characteristic (ROC) curve analysis further demonstrated that FGF21 exhibited good sensitivity and specificity for the discrimination of mild, moderate, and severe hepatic steatosis, suggesting its potential as a non-invasive biomarker for disease monitoring.