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Aim: The objective of this work is to find out whether there is a relation between the expression of TLR4 and fibrosis progression in chronic HCV patients. Background: Toll-like Receptor 4 (TLR4) is a pattern recognition receptor whose activation results in the production of several proinflammatory cytokines. Methods: Fifty patients with chronic HCV were included. They were divided into group A: 40 patients (F1-F4) and group B (control group) which included ten patients (F0) based on fibroscan value. All patients were exposed to clinical and laboratory evaluations preliminary to antiviral therapy, assessment of TLR4 mRNA by Real Time- PCR. Results: Twenty-eight males and 22 females with a mean age 28.9±6.1 years. The mean TLR4 expression is 11.2±7.4 folds, TLR4 expression in F0 group is 2.8±1.9, in F1 group 4.8±1.5, F2 group 10.2±2.5, F3 group 16.8±1.5 and in F4 21.3±3.6 folds (p<0.001). TLR4 showed a positive correlation with age, fibrosis stage, HCV RNA, serum transaminases, total bilirubin and prothrombin time, a negative correlation with platelet count and serum albumin. Fibrosis progression was independently associated with TLR4 expression (β=0. 648, P<0.0001), RNA (β= 0.160, P =0.001) and platelet count (β= -0.248, P = 0.004). Conclusion: The expression of TLR4 is highly correlated with the fibrosis progression; TLR4 may be a potential target for drugs to limit the progression of fibrosis. [ABSTRACT FROM AUTHOR]