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


Yalcinkaya I., EKİNCİ İ., Dumur S., Duran E. N., Uzun H., Yalcinkaya M., ...Daha Fazla

Journal of Clinical Medicine, cilt.15, sa.2, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 2
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/jcm15020559
  • Dergi Adı: Journal of Clinical Medicine
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
  • Anahtar Kelimeler: activating transcription factor 4, toll-like receptor 4, metabolic dysfunction-associated steatotic liver disease (MASLD), inflammatory pathways
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

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.