title: The impact of ledipasvir/sofosbuvir on patient-reported outcomes in cirrhotic patients with chronic hepatitis C: the SIRIUS study.
abstract: BACKGROUND
  Interferon- and ribavirin (RBV)-free regimens can improve patient-reported outcomes (PROs) during treatment.
  
  
  OBJECTIVE
  To compare PROs during treatment with ledipasvir and sofosbuvir (LDV/SOF) to placebo and to LDV/SOF + RBV.
  
  
  METHODS
  Treatment-experienced CH-C genotype 1 patients with compensated cirrhosis (N = 154) were randomized to receive 24 weeks of LDV/SOF or 12 weeks of placebo followed by 12 weeks of LDV/SOF + RBV (the SIRIUS clinical trial). While blinded to their HCV RNA level and study treatment, patients completed PRO questionnaires (SF-36, FACIT-F, CLDQ-HCV, WPAI:SHP) at baseline, during and post-treatment.
  
  
  RESULTS
  Baseline PRO scores were similar between the two study arms. Patients receiving LDV/SOF showed improvement in a number of PROs (predominantly related to mental health) starting as early as 4 weeks after treatment initiation; no PRO decrement from baseline were noted, and no PRO scores were inferior to placebo (all P > 0.05). In the second 12 weeks, patients who were receiving LDV/SOF continued to improve PROs (up to +9.2% from a 100% maximum possible score, P < 0.05), while patients receiving LDV/SOF + RBV had less gains or no improvement in their PRO scores. However, regardless of the regimen, patients who successfully cleared the virus (N = 149) had significant improvement in all aspects of PROs (up to +12.2% by post-treatment week 12, up to +16.9% by week 24).
  
  
  CONCLUSIONS
  Treatment-experienced cirrhotic patients experience a notable improvement of their PROs during treatment with LDV/SOF. Furthermore, achieving SVR-12 is associated with significant PRO improvement, which further improves at post-treatment week 24 in this difficult to treat group of patients with chronic hepatitis C.
authors.affiliation: Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.|Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.|Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.affiliation: Department of Hepatology, Hôpital Cochin et Université Paris-René Descartes, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: CHU de Nancy-Hôpital Brabois Adulte, Vandoeuvre-lès-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: INSERM, UMR912 (SESSTIM), Marseille, France.|UMR_S912, IRD, Aix Marseille Université, Marseille, France.|ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France.
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Carrieri
authors.affiliation: Hôpital Saint Joseph, Marseilles, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; 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; D063868:Patient Outcome Assessment; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: HCV; HRQL; LDV/SOF; patient-reported outcomes