title: Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials.
abstract: Cure rates above 90% have been reported in most Phase III clinical trials using distinct all-oral direct-acting antivirals (DAAs) in chronic hepatitis C patients. Preliminary results in real-world patients have confirmed this, although efficacy tends to be lower.
  
  
  
  All consecutive chronic hepatitis C patients treated with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined. Host and viral factors were tested as predictors of treatment failure.
  
  
  
  A total of 363 chronic hepatitis C patients had completed a course of all-oral DAA therapy outside clinical trials up to the end of 2015. All but 14 (4%) patients achieved sustained virological response. There were 10 failures that occurred after 12 weeks of sofosbuvir-ledipasvir, despite 5 of them being on ribavirin. All failures but one were relapses. The only patient with viral breakthrough selected NS5B L159F and NS5A Y93H. In multivariate analyses, only advanced liver fibrosis (Metavir F3-F4) and HIV coinfection were significantly associated with treatment failure. A trend towards lower response was seen for HCV genotype 4.
  
  
  
  Treatment failures outside clinical trials are roughly seen in 4% of chronic hepatitis C patients who complete a course of all-oral DAA therapy, resembling what is seen in registration trials. In our series, outcomes were not significantly influenced by ribavirin addition, IL28B polymorphisms, HCV genotype, high baseline HCV RNA or prior interferon failure. However, advanced liver fibrosis and HIV coinfection were significantly associated with treatment failure. Our findings support that there is still room for individualization of current DAA therapy.
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arias
authors.affiliation: Microbiology Department, Santiago University & Conxo-CHUS Hospital, Santiago de Compostela, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aguilera
authors.affiliation: Infectious Diseases Unit, La Paz University Hospital & Autonomous University, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Benítez-Gutiérrez
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Lledó
authors.affiliation: Microbiology Department, Santiago University & Conxo-CHUS Hospital, Santiago de Compostela, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navarro
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.affiliation: Department of Internal Medicine, Conxo-CHUS Hospital, Santiago de Compostela, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Otero
authors.affiliation: Infectious Diseases Unit, La Paz University Hospital & Autonomous University, Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Peña
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Cuervas-Mons
authors.affiliation: Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D060085:Coinfection; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D000069474:Sofosbuvir; D017211:Treatment Failure; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C000595958:ledipasvir, sofosbuvir drug combination; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir