title: Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development.
abstract: BACKGROUND
  Therapeutic options for patients with HCV-related liver disease have increased over the last two decades. In fact, the old standard of care based on the combination of pegylated interferon and ribavirin did not result in satisfactory eradication rates, particularly in patients with liver cirrhosis. With the advent of direct-acting antivirals (DAAs), higher rates of viral clearance became possible and, patients with contraindications to interferon obtained access to treatment. However, several concerns have been raised regarding first-generation DAAs, namely their high costs, and the emergence of resistant-associated variants with low susceptibility to these drugs.
  
  
  METHODS
  In this review, the authors discuss the data about the efficacy and safety of the main anti-HCV direct-acting antivirals currently in the pipeline. Furthermore, they evaluate the impact of these drugs on the therapeutic options currently available for HCV patients.
  
  
  CONCLUSIONS
  The results of trials evaluating the effectiveness of new DAAs are encouraging. These new antivirals lead to high rates of viral eradication without relevant adverse reactions and seem to be effective regardless of viral genotypes, presence of resistant-associated variants or advanced liver disease. Consequently, with the advent of this new family of drugs, chronic HCV-related hepatitis may become a curable disease.
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gentile
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Scotto
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Zappulo
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Antonio Riccardo
authors.initials: AR
authors.lastname: Buonomo
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Pinchera
authors.affiliation: a Department of Clinical Medicine and Surgery , University of Naples 'Federico II' , Naples , Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Borgia
mesh_terms: D000577:Amides; D000998:Antiviral Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use; D001572:Benzofurans / Q000627:therapeutic use; D002219:Carbamates; D003521:Cyclopropanes; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001552:Benzazepines; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D015507:Drugs, Investigational; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D011810:Quinoxalines; D000069474:Sofosbuvir; D013449:Sulfonamides; 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; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir; C571889:asunaprevir
keywords: HCV; cirrhosis; elbasvir; grazoprevir; resistance; sofosbuvir; velpatasvir