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Gastroenterology. 2018 Oct 17. pii: S0016-5085(18)35155-2. doi: 10.1053/j.gastro.2018.10.024. [Epub ahead of print]

Status of Direct-acting Antiviral Therapy for HCV Infection and Remaining Challenges.

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Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France, Université de Strasbourg, Strasbourg, France, Pôle Hépato-digestif, Institut Hospitalo-Universitaire, Nouvel Hôpital Civil, Strasbourg, France. Electronic address:
Section of Hepatology, Clinic for Gastroenterology and Rheumatology; University Clinic Leipzig, Leipzig, Germany.
Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven Connecticut, USA.
Department of Medicine, University of Florida, Gainesville, FL, USA. Electronic address:


Chronic infection with hepatitis C virus (HCV) is a major cause of liver disease and hepatocellular carcinoma worldwide. Following the discovery of HCV 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized care of patients, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for HCV infection and discuss remaining challenges. We highlight licensed compounds, discuss the potential to shorten therapy even further, and review different options for treatment failure and resistance. We also provide an overview on clinical experience with generic agents and evidence for their efficacy. Finally, we discuss the need for new drugs and outline promising targets for future therapies.


direct acting antivirals; hepatitis C; resistance; treatment failure

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