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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> Both TLR4 (<i>p</i> = 0.010) and ATF4 (<i>p</i> < 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, <i>p</i> < 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, <i>p</i> = 0.01), indicating limited discriminative ability. <b>Conclusions:</b> 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.