For almost a decade the standard of care (SOC) therapy in patients with chronic hepatitis C virus (HCV) infection has consisted of a 24-48 week course of pegylated interferon-alpha in combination with ribavirin. This therapy is associated with significant adverse effects and leads to sustained virological response (SVR) in only 50% of patients with genotype 1. The development of compounds with direct antiviral activity (DAAs) against HCV genotype 1 during the past 10 years has led to the most significant breakthrough since the virus was first identified in 1989, Leading to a real revolution in the treatment of chronic HCV infection. The combination of the new DAAs with the SOC therapy has led to a significant improvement in achieving SVR in treatment-naïve (30%), as well as in treatment-experienced patients with genotype 1 (24-64%, depending on the response to previous antiviral treatment). In addition, treatment with DAAs enables shortening therapy in certain subgroups of patients, without compromising the SVR rate. However, the new treatment is challenging as it is associated with more severe adverse effects, complicated treatment regimens, need for frequent monitoring, drug-drug interaction, tolerance problems and development of selected resistant strains. This review updates the current information regarding DAAs, the new challenges that we will have to face and the therapeutic horizon in the near future.
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