INTRODUCTION: Studying the predictors of SVR to pegylated interferon (PEG-INF) alfa-2a and ribavirin (RBV) therapy in chronic HCV infected patients is crucial for selecting those who would benefit most from therapy. Increased HPCs in HCV-infected patients were shown to be correlated with increasing fibrosis and response to treatment. HPCs could be detected in the liver by immunohistochemical expressions of cytokeratin (CK) 7 and CK19. AIMS&METHODS: a. Evaluate the response rate to interferon based treatment in chronic HCV patients. b. Detect the predictors of SVR to treatment. c. Study the correlations between CK7 and CK19 expressions and treatment response. This study included 483 chronic HCV infected patients who fulfilled the study criteria who underwent clinical, biochemical and virological assessments before treatment and at 12, 24, 48 and 72 weeks post-treatment. Only 330 patients; 193 male and 137 completed the course and were included in the statistical analysis. Only 50 specimens were examined for CK7 and CK19 expression using avidin, biotin, peroxidase technique. RESULTS: End of treatment virologic response (ETVR) was achieved in 70% of patients, while 30% were non responders. SVR was higher in females whereas most of male patients didn't achieve SVR (P<0.01). Patients with SVR were significantly younger (P<0.004) and had lower body weight (P<0.001). There was significant inverse relation between SVR and aspartate aminotransferase (AST) and alpha feto-protein (AFP); P<0.000 for each. The independent predictors of SVR were younger age and lower AST (P<0.02 for each). There was significantly positive correlation between the grade of necro-inflammatory activity, AST and AFP and the stage of hepatic fibrosis (P<0.003, P<0.000 & P< 0.000 respectively). There was significant association between CK7 and/or CK19 expressions and grade of necroinflammation (P<0.033, 0.026 respectively), and/or advanced stage of fibrosis (P<0.001, 0.000 respectively). There were significant inverse relations between SVR and stage of hepatic fibrosis (P<0.001), and CK19 expression (P<0.000). CONCLUSION: Forty % of patients with chronic HCV who completed the course of combination therapy achieve SVR. Younger age and lower pre-treatment AST are independent predictors of SVR. HPCs as assessed by CK7 and CK19 expressions may be incorporated in assessment of treatment response of these patients