Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients

Abstract

Background and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 gene polymorphism on the progression of HBV-linked liver diseases (liver cirrhosis and HCC). Methods. In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR. Results. IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p<0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p=0.03, OR = 2.45, and 95% CI: 1.69–3.65), IL-6 levels (p=0.04, OR = 3.45, and 95% CI: 2.01–6.9), and TRL2 variants (p=0.01, OR = 4.25, and 95% CI: 2.14–13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion. In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.