Metabolic Dysfunction-Associated Steatotic Liver Disease: The Associations between Inflammatory Markers, TLR4, and Cytokines IL-17A/F, and Their Connections to the Degree of Steatosis and the Risk of Fibrosis.

ABSTRACT

Background: The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease) is driven by environmental, genetic, metabolic, immune, and inflammatory factors. IL-17 and TLR4 determine hepatic steatosis, inflammation, and finally fibrosis. Objectives: To explore the associations between the plasma levels of inflammatory markers, TLR4, and the cytokines IL17A/F, as well as their connections with the degree of hepatic steatosis and the risk of hepatic fibrosis (defined by the FIB-4 score) in MASLD patients. Methods: The study cohort included 80 patients diagnosed with MASLD. The IL-17A/F and TLR4 serum concentrations were determined using the ELISA method. Results: We found a significant difference in the CAR levels (C-reactive protein to albumin ratio) when comparing MASLD patients with severe steatosis to those with mild/moderate steatosis (Student's t test, t (71) = 2.32, p = 0.023). The PIV (pan-immune inflammatory value) was positively correlated with the SII (systemic immune inflammation index), (r = 0.86, p < 0.0001) and the CAR (r = 0.41, p = 0.033) in MASLD patients with severe steatosis. In contrast, increased values of the LMR (lymphocyte to monocyte ratio) were significantly associated, with decreased levels of the SII (ρ = -0.38, p = 0.045). We also found a positive correlation between the CAR and the SII (r = 0.41, p = 0.028). In patients with mild/moderate steatosis, a significant positive correlation was observed between the SII and IL17A (r = 0.36, p = 0.010), the PIV and the CAR (r = 0.29, p = 0.011), the PIV and the SII (r = 0.87, p < 0.0001) and the PIV and IL17A (r = 0.3, p = 0.036). A negative correlation was observed between the LMR and the SII (r = -0.55, p < 0.0001) and the CAR and IL17F (r = -0.37, p = 0.011). Regarding the inflammatory markers, the PIV (336.4 vs. 228.63, p = 0.0107), and the SII (438.47 vs. 585.39, p = 0.0238) had significantly lower levels in patients with an intermediate-high risk of hepatic fibrosis as compared with the patients with a low risk of hepatic fibrosis. The PNI (prognostic nutritional index) (47.16 vs. 42.41, p = 0.0392) had significantly different levels in patients with the likelihood of hepatic fibrosis than those with a low risk of hepatic fibrosis. Conclusions: Regarding the inflammatory markers, the PIV and the SII hold promise as biomarkers for discriminating between MASLD patients with an intermediate-high risk and those with a low risk of hepatic fibrosis. Our findings underscore the role of IL-17A and its potential relationship with inflammatory markers in MASLD pathogenesis and the progression to hepatic fibrosis.