# 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.

## Key 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.