title: Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.
abstract: Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.
authors.affiliation: Gastroenterology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Riveiro-Barciela
authors.affiliation: Digestive Diseases Service, Hospital 12 Octubre, Madrid.
authors.forename: I
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Rincón
authors.affiliation: Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Real
authors.affiliation: Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Llerena
authors.affiliation: Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Gea
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Hospital Universitario La Paz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Olveira
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Liver Unit, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Carrillo
authors.affiliation: Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Polo
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Carrión
authors.affiliation: Hospital Universitario Donostia, Donostia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Devesa
authors.affiliation: Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Baliellas
authors.affiliation: Hospital Universitario de A Coruña, A Coruña, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Castro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Hospital Virgen de Valme, and Institute of Biomedicine of Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: H. U. de Gran Canaria Dr. Negrín, Gran Canaria, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Granados
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|H. U. Virgen del Rocío, Seville, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Pascasio
authors.affiliation: Hepatology Unit, Digestive Medicine Service, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rubín
authors.affiliation: H. U. San Cecilio, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Salmeron
authors.affiliation: Hospital Universitario de Burgos, Burgos, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Badia
authors.affiliation: C. H. U. de Albacete, Albacete, Spain.
authors.forename: J M M
authors.initials: JM
authors.lastname: Planas
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.|Liver Unit, Hospital Clínic, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lens
authors.affiliation: Department of Gastroenterology, Complejo Hospitalario Universitario de Pontevedra and IISGS, Pontevedra, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Turnes
authors.affiliation: Hospital Reina Sofia, Córdoba, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Montero
authors.affiliation: Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Buti
authors.affiliation: Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Esteban
authors.affiliation: Gastroenterology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: C M
authors.initials: CM
authors.lastname: Fernández-Rodríguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: SVR12; cirrhosis; daclatasvir; genotype 3; hepatitis C; ledipasvir; observational study; real-world cohort; sofosbuvir