Metabolic Characteristics and Cytokine Gene Polymorphisms as Potential Risk Factors for a Higher Liver Fibrosis Stage...

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 IL17 (A7448G and G197A) and TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms are associated with increased liver fibrosis stages in MASLD patients. Genotyping for the IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile 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 (p = 0.006), lipid metabolism (total cholesterol, HDL cholesterol, triglycerides), and the severity of liver fibrosis (p < 0.05). The IL17A-G197A 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 p = 0.0423). In the multivariable ordinal logistic regression, the IL17A-G197A polymorphism remained significantly associated with higher liver fibrosis stages (adjusted p = 0.0155). Patients with the dominant genotype (GA + AA) of the IL17A-G197A 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 IL17-related genetic polymorphisms and metabolic characteristics significantly affect liver fibrosis progression in MASLD patients, with the IL17A-G197A gene polymorphism identified as an independent multivariate predictor of fibrosis progression.