title: Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.
abstract: The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Jiménez-Pérez
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Grande
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: España Contreras
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pinazo Martínez
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: de la Cruz Lombardo
authors.affiliation: Miguel Jiménez-Pérez, UGC de Aparato Digestivo, Unidad de Hepatología-Trasplante Hepático, Hospital Universitario Regional de Málaga, 29010 Malaga, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Olmedo Martín
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Direct-acting antivirals; Hepatitis C virus; Resistance; Treatment