title: Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort.
abstract: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice.
  
  
  
  Data from HCV genotype 1 patients treated with either OMV/PTV/r+DSV±ribavirin (RBV) (n=1567) or LDV/SOF±RBV (n=1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded.
  
  
  
  The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV±RBV and 95.8% with LDV/SOF±RBV. No significant differences were observed in SVR according to HCV subgenotype (p=0.321 [OMV/PTV/r+DSV±RBV] and p=0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV±RBV] and p=0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p<0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r+DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%.
  
  
  
  In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r+DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles.
  
  
  
  In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex.
authors.affiliation: Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid and CIBERehd, Madrid, Spain. Electronic address: joseluis.calleja@uam.es.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Hospital Universitario Marques de Valdecilla, IDIVAL, Santander and Facultad de Medicina, Universidad de Cantabria, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Rincón
authors.affiliation: Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ruiz-Antorán
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Christie
authors.initials: C
authors.lastname: Perelló
authors.affiliation: Hospital Universitario Ramon y Cajal, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gea
authors.affiliation: Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Lens
authors.affiliation: Hospital Universitario La Paz, CIBERehd, IdiPAZ, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Samaniego
authors.affiliation: Hospital San Pedro, Logroño, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Sacristán
authors.affiliation: Hospital Universitario La Fe and CIBERehd, Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Eliz
authors.affiliation: Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Cantabria, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Llerena
authors.affiliation: Hospital Universitario Virgen del Rocío and CIBERehd, Seville, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Pascasio
authors.affiliation: Complejo Hospitalario Universitario de Pontevedra and IISGS, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Turnes
authors.affiliation: Hospital Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Torras
authors.affiliation: Hospital Germans Trias I Pujol and CIBERehd, Badalona, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Morillas
authors.affiliation: Hospital Universitario Vall D'Hebrón, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Llaneras
authors.affiliation: Hospital Clínico de Valencia, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Serra
authors.affiliation: Hospital Universitario General de Valencia, Valencia, Spain.
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.affiliation: Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: Conrado Fernández
authors.initials: CF
authors.lastname: Rodriguez
authors.affiliation: Hospital Universitario Virgen del Rocío, IBIS and CIBERehd, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: Complejo Asistencial Universitario León, León, IBIOMED and CIBERehd, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Jorquera
authors.affiliation: Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Simon
authors.affiliation: Hospital Universitario Donostia, San Sebastian, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Carmen Alvarez
authors.initials: CA
authors.lastname: Navascues
authors.affiliation: Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Bañares
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Hospital Universitario Ramon y Cajal, Madrid, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Albillos
authors.affiliation: Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño
mesh_terms: D015081:2-Naphthylamine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D002219:Carbamates / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D015331:Cohort Studies; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage; D005838:Genotype; D005919:Glomerular Filtration Rate; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology*; D006801:Humans; D047029:Lactams, Macrocyclic; D008113:Liver Neoplasms / Q000209:etiology; D047028:Macrocyclic Compounds / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D011392:Proline / Q000031:analogs & derivatives; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage; D000069474:Sofosbuvir; D013030:Spain; D013449:Sulfonamides / Q000008:administration & dosage; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives; D014633:Valine; D055815:Young Adult
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D003521:Cyclopropanes; D005449:Fluorenes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C000595958:ledipasvir, sofosbuvir drug combination; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014542:Uridine Monophosphate; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir; D000069474:Sofosbuvir
keywords: Antiviral agents; Dasabuvir; Genotype 1; Hepatitis C, Chronic; Ledipasvir; Ombitasvir; Paritaprevir; Randomized controlled trials; Real-world; Ritonavir; Sofosbuvir; Sustained virologic response