Diagnostic Value of Serum Fibroblast Growth Factor 21 Combined with Fibrosis-4 Index for Hepatic Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease

Abstract

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, with significant fibrosis (≥F2) strongly associated with adverse outcomes. The current study evaluated the diagnostic value of serum fibroblast growth factor 21 (FGF-21) combined with the fibrosis-4 index (FIB-4) for the assessment of hepatic fibrosis in patients with MASLD.

Materials and Methods: A total of 125 patients with MASLD were enrolled (91 patients with F0-F1 fibrosis and 34 patients with F2-F4 fibrosis). Independent risk factors for significant fibrosis were identified using multivariate logistic regression. A combined diagnostic model was developed and validated using bootstrap resampling (500 iterations). Diagnostic performance was evaluated using receiver operating characteristic curve analysis.

Results: Compared to the F0-F1 fibrosis group, patients with F2-F4 fibrosis had significantly higher waist circumference (WC), gammaglutamyl transferase (GGT), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, FIB-4 index, and FGF-21 levels and significantly lower high-density lipoprotein cholesterol (HDL-C) levels. Multivariate analysis identified FIB-4, FGF-21, WC, GGT, and HOMA-IR as independent risk factors, whereas HDL-C was identified as a protective factor. The combined model achieved an area under the curve of 0.806 (95% CI: 0.727-0.886), outperforming FIB-4 (0.743) and FGF-21 (0.735) alone. At the optimal cutoff determined by the Youden index, the combined model maintained comparable specificity while significantly improving sensitivity to 94.12%. The model also demonstrated balanced performance under both specificity-driven and sensitivitydriven strategies.

Conclusion: Combining FGF-21 with FIB-4 improved diagnostic accuracy for significant fibrosis in MASLD, providing a practical, noninvasive tool for early risk assessment and patient stratification.

Cite this article as: Cao Y, Zhang X, Zhang Q. Diagnostic value of serum fibroblast growth factor 21 combined with fibrosis-4 index for hepatic fibrosis in metabolic dysfunction–associated steatotic liver disease. Turk J Gastroenterol. 2026;37(7):782-792.