Introduction:The progression of fibrosis in chronic hepatitis C (CHC) is a multifactorial process. The high adverse effects and the cost of standard health care increase the demand to discover new predictors for the progression of fibrosis in CHC patients. Our study aims to establish the relation between the angiogenic marker [vascular endothelial growth factor (VEGF)] and activated hepatic stellate cells (HSCs) represented by the expression of -smooth muscle actin (-SMA) and whether these 2 markers can be used as predictors for the progression of fibrosis in patients with CHC.Materials and Methods:Histopathologic and immunohistochemical analyses were used for examining the morphology and the expression of VEGF and -SMA in 60 CHC biopsies procured from CHC patients. Multivariate analysis was used to correlate the protein expression with staging and grading of liver fibrosis. Cutoff values of -SMA and VEGF were determined by the receiver operating characteristics curve.Results:There was a positive correlation between VEGF and HSCs expressing -SMA (=0.287, P=0.026) and both factors were correlated with the stage of fibrosis (P<0.001). Using the receiver operating characteristics curve, both VEGF (area under the curve=0.71, P<0.006) and -SMA (area under the curve=0.82, P<0.001) were positive predictors for moderate and severe fibrosis.Conclusions:This study demonstrates the relation between VEGF expression and the activated HSCs denoted by the expression of -SMA in CHC biopsies and together can be used as a predictor for the progression of fibrosis.