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

J Hepatol. 2015 Aug;63(2):337-45. doi: 10.1016/j.jhep.2015.03.014. Epub 2015 Mar 17.


Background & aims: 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.

Keywords: Direct acting antivirals; Fatigue; Fibrosis; HCV; Health-related quality of life; Patient reported outcomes; Ribavirin; Work productivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage
  • Benzimidazoles / administration & dosage*
  • DNA, Viral / genetics*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Fluorenes / administration & dosage*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / etiology*
  • Male
  • Middle Aged
  • Quality of Life*
  • Sofosbuvir / administration & dosage*
  • Surveys and Questionnaires


  • Antiviral Agents
  • Benzimidazoles
  • DNA, Viral
  • Fluorenes
  • ledipasvir
  • Sofosbuvir