Diagnostic Utility of Serum Activating Transcription Factor 4 and Toll-like Receptor 4 as Early Biomarkers of Inflammation in Metabolic Dysfunction–Associated Steatotic Liver Disease

TL;DR

This study found that higher levels of ATF4 in the blood can help detect early signs of liver disease linked to metabolic issues.

Contribution

The study identifies ATF4 as a strong early biomarker for metabolic dysfunction–associated steatotic liver disease.

Findings

MASLD patients had significantly higher serum ATF4 and TLR4 levels compared to healthy controls.

ATF4 showed high sensitivity and specificity for diagnosing MASLD with an AUC of 0.968.

TLR4 had limited discriminative ability with lower sensitivity and specificity compared to ATF4.

Abstract

Background/Objectives: This study aimed to evaluate the serum activating transcription factor 4 (ATF4) and toll-like receptor 4 (TLR4) levels in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), and to explain the mechanism in the inflammatory and fibrogenic signaling pathways that are thought to play a role in the development of MASLD through these parameters. Methods: Eighty-eight patients with MASLD and 88 age-sex matched healthy controls were included in this study. Serum ATF4 and TLR4 concentrations were measured using an ELISA method. Results: Both TLR4 (p = 0.010) and ATF4 (p < 0.001) levels were higher in the MASLD group. In this group, TLR4 showed a negative correlation with age. ROC analysis indicated that an ATF4 value of 1.305 or above identified MASLD with 93.2% sensitivity and 85.2% specificity (AUC = 0.968, p < 0.001). For TLR4, a cut-off of 343.5 yielded a sensitivity of 54.5% and a specificity of 70.5% (AUC = 0.613, p = 0.01), indicating limited discriminative ability. Conclusions: Patients with MASLD had higher serum TLR4 and ATF4 levels, consistent with their involvement in inflammatory and fibrotic pathways. ATF4 showed strong diagnostic performance and may serve as a useful non-invasive marker for early MASLD. When evaluated together with TLR4, it may provide complementary information regarding inflammatory pathway activation.

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