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Background: Racial differences and broad spectrum response to anti-hepatitis C (anti-HCV) therapy suggest a possible role for host genetic diversity in treatment outcomes. We aim to determine the association and predictive value of certain human leukocyte antigen (HLA) class I alíeles with either susceptibility to viral clearance or persistence following pegylated interferon (Peg-IFN) plus ribavirin therapy in chronic hepatitis C (HCV) genotype 4 patients in Egypt. Methods: This study included 200 unrelated chronic HCV patients who received Peg-IFN plus ribavirin therapy [112 patients with sustained virological response (SVR) and 88 non-responders (NR)]. Serological testing of HLA class I antigens (HLA-A and HLA-B alíeles) were performed by standard complement-dependent microlymphocytotoxicity assay. Results: The frequency of HLA-A01 was significantly higher in SVR than in NR cases [OR: 0.51 ; 95% CI: 0.27-0.981 ; P = 0.042], while the frequency of alíeles B38 (P = 0.011), B40 (P < 0.001) and B41 (P < 0.001) was significantly higher in NR cases (OR/95% CI: 7.05/ (1.39-18.01), 10.31/3.14-36.1 . On logistic regression analysis, presence of the HLA-A01 alíele was associated with SVR (OR: 0.50; 95% CI: 0.28-0.89; P= 0.02) and HLA-B38 can predict non response to therapy (OR: 7.92; 95% CI: 1.67-37.54; P = 0.009) with an overall accuracy of 60%.Severe fibrosis (OR: 3.035; 95% CI: 1.521-6.091; P= 0.002), high viremia (OR: 2.69; 95% CI: 1.11-6.53; P= 0.005) and steatosis (OR: 2.1 ; 95% CI: 1.002-3.90; P = 0.041 ) predicted no response with an overall accuracy of 81.8%. Conclusion: HLA-A01 and HLA-B38 alíeles are associated with and may have a role in the outcome of response to Peg-IFN plus ribavirin therapy in Egyptian patients diagnosed with chronic HCV infection. The use of immunologie markers to predict the outcome of treatment may help pharmacogenetic personalization of treatment for HCV infection. [ABSTRACT FROM AUTHOR]