title: Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection.
abstract: OBJECTIVE
  The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens.
  
  
  METHODS
  From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ.
  
  
  RESULTS
  A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTDand ≥LLOQ, SVR12was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association)0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004.
  
  
  CONCLUSIONS
  TW4-response indicates the probability of achieving SVR12to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting.
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Unit of Infectious Pathology, Hospital Universitario Alvaro Cunqueiro, Vigo, Spain.
authors.forename: L E
authors.initials: LE
authors.lastname: Morano-Amado
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Granados
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Macías
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital La Línea, AGS Campo de Gibraltar, La Linea de la Concepcion, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Téllez
authors.affiliation: Unit of Infectious Diseases, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: García-Deltoro
authors.affiliation: Unit of Infectious Diseases, Hospital Virgen Macarena, Seville, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ríos
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario Torrecárdenas, Almeria, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Collado
authors.affiliation: Unit of Infectious Diseases, Hospital Regional de Málaga, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Delgado-Fernández
authors.affiliation: Fundación Biomédica del Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Suárez-Santamaría
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Unit of Infectious Pathology, Hospital Universitario Alvaro Cunqueiro, Vigo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Miralles-Álvarez
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. Electronic address: karin.neukam@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Neukam
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D002219:Carbamates; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000494:pharmacology; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011759:Pyrrolidines; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000494:pharmacology; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011759:Pyrrolidines; C586541:ledipasvir; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Cirrhosis; Direct-acting antivirals; Hepatitis C virus genotype 3; Interferon-free regimens; Sustained virological response; Viral kinetics