title: Daclatasvir-containing all-oral regimens for the treatment of hepatitis C virus infection.
abstract: The treatment of chronic hepatitis C is revolutionizing rapidly. The aim of this study is to review the efficacy and safety of daclatasvir (DCV)-containing all-oral regimens in clinical studies for chronic hepatitis C treatment. Using PubMed and search terms of 'DCV,' 'hepatitis C virus (HCV) treatment,' and 'HCV NS5A inhibitors,' literature on the clinical development of DCV, as well as abstracts presented at the April 2015 annual meeting of the European Association for the Study of the Liver (EASL) and November 2014 annual meeting of the American Association for the Study of Liver Diseases were reviewed. The final search was undertaken on 14 July 2015. With its potent antiviral activity to all HCV genotypes (GT) demonstrated in preclinical, phases 1-3 studies, DCV has been acting as a very competent team player in clinical trials of all-oral regimens. It is generally safe and well tolerated with a low genetic barrier to resistance and low potential for drug-drug interaction. Administered with a non-structural protein 3 (NS3) protease inhibitor (asunaprevir, ASV) with or without a non-nucleoside NS5B polymerase inhibitor (beclabuvir, BCV), or a nucleotide NS5B polymerase inhibitor (sofosbuvir, SOF), DCV is able to achieve greater than a 90-% HCV eradication rate in both treatment-naïve and treatment-experienced patients with GT 1. A triple combination regimen with DCV/ASV/BCV results in 100% sustained virologic response (SVR) rates in HCV GT 4 treatment-naïve subjects. DCV/SOF combination also had demonstrated up to 90-% SVR rates in GT 3-infected non-cirrhotic patients. The efficacy and safety of DCV-containing all-oral regimens highlight a new era of interferon-free therapy for chronic hepatitis C.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sec 4, Taichung, Taiwan. yansh@vghtc.gov.tw.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. yansh@vghtc.gov.tw.|Department of Nursing, Central Taiwan University of Science and Technology, Taichung, Taiwan. yansh@vghtc.gov.tw.
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan. kaojh@ntu.edu.tw.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D002219:Carbamates; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: C587012:8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; D000998:Antiviral Agents; D001552:Benzazepines; D002219:Carbamates; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir; D000069474:Sofosbuvir
keywords: Daclatasvir; Genotype; Hepatitis C virus; Interferon; NS5A inhibitor