Molecular profiling is uprising as a BIBN 4096 pharmacogenetic tool to predict treatment outcome in chronic hepatitis C as a way towards personalized therapy. Emerging evidence suggests that miRNAs have an intense impact on the clinical outcome of standard INF therapy. Pretreatment hepatic miRNA expression pattern in CHC patients revealed that the expression levels of miR-34b, miR-145, miR-143, miR-652, and miR-18a were significantly higher in non-responder than SVR patients, while BMS 195614 miR-27b, miR-422b, and miR-378 expression levels were higher in SVR than NR patients. Increased pretreatment levels of serum miR- 122 were correlated with early response and SVR, while reduced hepatic baseline miR-122 levels were associated with poor response to INF therapy. INF-induced miRNAs were reported to be differentially expressed in peripheral blood mononuclear cells from CHC genotype 1 or 2 patients and might affect the response to INF therapy. However, little is known about INF-related miRNAs regarding their detection in serum, their correlation with clinical data, and their potential use as non-invasive diagnostic and prognostic biomarkers in CHC. Thus, in order to gain further insights into the genetic factors that may affect treatment outcome in CHC; it is interesting to examine pretreatment expression profiles of circulating INFrelated miRNAs, in particular, miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296, previously reported to be induced by INFs in different in vitro models. We investigated the expression profiles of these selected miRNAs as novel biomarkers in serum of CHC genotype 4 patients, their correlations with clinical data, and whether their pretreatment levels would predict patient response to PEG-IFN-��/RBV therapy. Our study revealed that the profiling results could be implicated as novel non-invasive diagnostic and prognostic pharmacogenetic biomarkers for treatment personalization in CHC and could also be used to identify new miRNA-based antiviral therapeutics. Understanding pretreatment miRNA profiles associated with therapeutic response to standard therapy for CHC would be a critical pharmacogenetic tool for personalizing therapy for NR patients. To the best of our knowledge, no one has examined the expression profiles of serum INF-related miRNAs in CHC genotype 4 patients and their relation to virological response to INF-based therapy. HCV-4 was chosen for this investigation since it is the predominate genotype in Egypt, resistant to treatment, and responsible for the majority of HCV infections worldwide, as previously reported. We used real-time PCR custom array technology as a powerful tool to estimate serum miRNAs. Quantitative PCR was advantageous over microarray by its high sensitivity, accuracy, lower cost, and lower sample requirements. All studied miRNAs were differentially expressed in sera from CHC patients and could discriminate CHC from controls by ROC analysis, suggesting that these miRNAs could serve as surrogate markers of CHC.