title: Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.
abstract: OBJECTIVE
  New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir.
  
  
  METHODS
  Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies.
  
  
  RESULTS
  There were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0-1 scale p<0.0001). During and post-treatment, HRQL remained lower in patients with advanced fibrosis. After achieving sustained virologic response, significant improvements from baseline in most HRQL domains were observed regardless of fibrosis stage (by 0.024-0.103 on a 0-1 scale; all p>0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to -0.056 in comparison with none-to-mild fibrosis, p<0.05). However, improvement of HRQL and work productivity after viral clearance was not related to the stage of fibrosis (all p>0.05).
  
  
  CONCLUSIONS
  Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis.
authors: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, United States; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States. Electronic address: zobair.younossi@inova.org.
authors: Zobair M
authors: ZM
authors: Younossi
authors: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for Outcomes Research in Liver Diseases, Washington, DC, United States.
authors: Maria
authors: M
authors: Stepanova
authors: Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors: Nezam
authors: N
authors: Afdhal
authors: Digestive Diseases Institute, Virginia Mason Clinic, Seattle, WA, United States.
authors: Kris V
authors: KV
authors: Kowdley
authors: Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: Center for Outcomes Research in Liver Diseases, Washington, DC, United States.
authors: Linda
authors: L
authors: Henry
authors: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States.
authors: Sharon L
authors: SL
authors: Hunt
authors: Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy, France.
authors: Patrick
authors: P
authors: Marcellin
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage*; D004279:DNA, Viral / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000069474:Sofosbuvir / Q000008:administration & dosage*; D011795:Surveys and Questionnaires
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004279:DNA, Viral; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir
keywords: Direct acting antivirals; Fatigue; Fibrosis; HCV; Health-related quality of life; Patient reported outcomes; Ribavirin; Work productivity