Metabolic Characteristics and Cytokine Gene Polymorphisms as Potential Risk Factors for a Higher Liver Fibrosis Stage in MASLD Patients: A Hospital-Based Study

Polymorphisms in the Toll-like receptor 4 (TLR4) and IL-17 cytokine genes play a role in liver fibrosis progression among patients with MASLD. The current study aimed to investigate whether the <i>IL17</i> (<i>A7448G</i> and <i>G197A</i>) and <i>TLR4</i> (<i>Asp299Gly</i> and <i>Thr399Ile</i>) gene polymorphisms are associated with increased liver fibrosis stages in MASLD patients. Genotyping for the <i>IL17F</i>-<i>A7488G</i>, <i>IL17A</i>-<i>G197A</i>, <i>TLR4</i>-<i>Asp299Gly</i>, and <i>TLR4</i>-<i>Thr399Ile</i> polymorphisms was performed on a sample of 42 MASLD patients and 39 healthy controls. Serum levels of IL17F, IL17A, and TLR4 were measured using ELISA techniques. Bivariate analysis revealed significant associations between glycemic levels (<i>p</i> = 0.006), lipid metabolism (total cholesterol, HDL cholesterol, triglycerides), and the severity of liver fibrosis (<i>p</i> < 0.05). The <i>IL17A</i>-<i>G197A</i> GA and AA genotypes were more frequent in patients with advanced liver fibrosis compared to those without fibrosis (GA genotype frequency: 42.9% vs. 7.7%; AA genotype frequency: 14.3% vs. 5.1%; adjusted <i>p</i> = 0.0423). In the multivariable ordinal logistic regression, the <i>IL17A</i>-<i>G197A</i> polymorphism remained significantly associated with higher liver fibrosis stages (adjusted <i>p</i> = 0.0155). Patients with the dominant genotype (GA + AA) of the <i>IL17A</i>-<i>G197A</i> polymorphism exhibited 3.91 times greater odds of experiencing at least a one-stage increase in liver fibrosis compared to those with the GG genotype (adjusted OR = 3.91, 95% CI: 1.33-12.34). This study indicates that <i>IL17</i>-related genetic polymorphisms and metabolic characteristics significantly affect liver fibrosis progression in MASLD patients, with the <i>IL17A</i>-<i>G197A</i> gene polymorphism identified as an independent multivariate predictor of fibrosis progression.