title: Current therapy for chronic hepatitis C: The role of direct-acting antivirals.
abstract: One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status. However, despite these remarkable achievements made in HCV drug discovery, challenges remain in the management of difficult-to-treat patients.
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: liguangdi.research@gmail.com.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Li
authors.affiliation: KU Leuven - University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Minderbroedersstraat 10, Leuven, 3000, Belgium. Electronic address: erik.declercq@kuleuven.be.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D057057:Serine Proteases / Q000737:chemistry / Q000187:drug effects; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000187:drug effects; D014764:Viral Proteins / Q000737:chemistry / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D057057:Serine Proteases; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C000614516:NS3-4A serine protease, Hepatitis C virus
keywords: Direct-acting antivirals; NS3/4A drugs; NS5A drugs; NS5B drugs