Abstract
Background Hepatitis B virus (HBV) chronically infects over several million people, often progressing to severe liver disease. Toll-like receptors (TLRs), notably TLR9, are critical for recognizing viral DNA and driving innate immune responses. Objective The objective of this study is to investigate the downregulation of TLR gene expression in HBV-infected patients, elucidating their role in innate immunity. Methodology A cohort of 434 HBV-positive patients was analyzed for TLR gene expression via real-time PCR. Results The HBV S genotype D (57.6%) was more prevalent than genotype C (42.4%) (p = 0.001). TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9 were significantly downregulated in both genotypes as compared to controls, with genotype D showing greater downregulation of TLR1, TLR5, TLR6, and TLR7 among HBV-positive patients. Conclusion Human TLR gene expression levels are downregulated due to HBV infection, with genotype D predominance suggesting differential immune regulation. These findings underscore the need for targeted HBV therapies informed by genotypic and immunological profiles.