Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Summary. During the late 1990s and early 2000s, major advances were made in the treatment of patients with chronic hepatitis C virus (HCV) infection. Interferon, combination interferon plus ribavirin (RBV) and pegylated interferon plus RBV increased sustained virologic response (SVR) rates from ∼5% to ∼40-80%, depending on the genotype of HCV infection. Advances in molecular biology have allowed investigators to begin to understand the mechanisms of HCV infection and replication. Advances in understanding of viral kinetics have provided tools to identify patients who are most likely to attain SVR. With the advances in the science of HCV infection, the first part of the 21st century has seen the development and early introduction of a number of direct-acting antiviral (DAA) drugs. These novel medications interfere with critical steps in HCV replication and have the potential to significantly increase SVR rates. This article will review the key elements of HCV replication and evaluate the various classes of new and investigational DAA that have the potential to create a revolution in the management of patients with chronic hepatitis C.