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Recently, genetic factors have been emphasized with the high predictive value of IL28B polymorphism [9]. It is http://www.selleck.cn/products/MK-1775.html remarkable that IFN-stimulated genes are highly expressed in non-responders; thus, pre-activation of the IFN system in patients appears to limit the effect of IFN therapy [10, 11]. Interestingly, new IFN-based triple therapies with second-wave protease inhibitors (simeprevir and faldaprevir), once a day, will soon be available making treatment easier and better tolerated [12-14]. However, the tolerability profile of triple therapy is still a concern with the side effects mostly related to IFN and RBV. Interestingly, in HCV genotype 1-infected patients without cirrhosis, simeprevir is being evaluated for a 12-week short treatment duration according to early virological response (Clinicaltrials.gov: NCT01846832). The development of new DAAs with different viral targets, nucleoside/nucleotide analogues and non-nucleoside inhibitors of the RNA-dependent RNA polymerase, and NS5A inhibitors http://www.selleckchem.com/PD-1-PD-L1.html is crucial. Impressive data have been reported with Simeprevir plus sofosbuvir with or without ribavirin in GT1 naive subjects and prior null responders (COSMOS study) [15]. Faldaprevir is being evaluated in IFN- free regimen [16]. Furthermore, faldaprevir plus deleobuvir plus PPI-668 (NS5A inhibitor) with or without ribavirin in persons with genotype 1a infection was studied [17]. Thirty-seven individuals with GT1a (without cirrhosis) were included. At week 4, HCV RNA was undetectable ( http://www.selleckchem.com/products/Adriamycin.html had undetectable HCV RNA. Recently, sofosbuvir (polymerase nucleotide inhibitor) (Sofosbuvir) has demonstrated an important antiviral efficacy, with a favourable safety profile [18-20], Sofosbuvir plus PEG-IFN and RBV for 12?weeks provide SVR of approximately 90% for HCV genotype 1-infected patients. Sofosbuvir plus RBV for 12?weeks provide excellent results for HCV genotype 2. For HCV genotype 3, sofosbuvir plus RBV for 24?weeks may be an option. Indeed, recent studies have demonstrated that antiviral combinations have additive antiviral potency with no cross resistance and a good safety profile. The ABT-333 (potent protease inhibitor) based regimen provides high antiviral potency with a favourable safety profile [21]. The high majority of HCV genotype 4-infected patients remain treated with PEG-IFN plus RBV therapy, we urge for trials with DAAs in this specific population [22]. These new DAA combination regimens with a finite duration and without IFN, available in a near future, would make the hope that HCV might be the first chronic viral infection eradicated worldwide. Thus, clinicians have turned their attention to an exciting new direction: investigating interferon free therapies that will be effective in all genotypes.