title: Effects of Viral Eradication With Ledipasvir and Sofosbuvir, With or Without Ribavirin, on Measures of Fatigue in Patients With Chronic Hepatitis C Virus Infection.
abstract: OBJECTIVE
  Fatigue is a disturbing symptom of chronic hepatitis C virus (HCV) infection. We assessed the effects of sustained virologic response 12 weeks after the end of therapy (SVR12) on fatigue.
  
  
  METHODS
  We performed a retrospective analysis of 100 patients with chronic HCV infection who achieved an SVR12 after treatment with ledipasvir and sofosbuvir, with or without ribavirin. Data were collected on fatigue-related patient-reported outcomes (PROs) and assessed by using the Functional Assessment of Cancer Therapy-Fatigue scoring system and the Vitality subscale of Short Form 36. We measured levels of cytokines and growth factors in frozen serum samples collected at baseline, week 12 of treatment, and 4 weeks after treatment. Central fatigue and peripheral or muscle fatigue (PF) were determined by using items from PROs. Serum levels of cytokines, growth factors, serotonin, alanine aminotransferase, and aspartate aminotransferase were measured by using the Bio-Plex, enzyme-linked immunosorbent, and enzymatic assays.
  
  
  RESULTS
  Compared with baseline, 4 weeks after the end of treatment, all fatigue-associated PROs improved significantly. Baseline PROs correlated inversely with serum level of interferon-γ; level of platelet-derived growth factor correlated with PF, central fatigue, and total fatigue score. Only PF correlated with serum level of serotonin. At baseline, high PF scores correlated with high serum levels of serotonin and low levels of interleukin-10 and tumor necrosis factor-α. In multivariate analysis, serum level of interleukin-8 was associated with greater fatigue (P < .02). Reductions in levels of chemokine (C-C motif) ligand 2 (also called monocyte chemotactic protein 1) were associated with fatigue after treatment (P = .0165).
  
  
  CONCLUSIONS
  In an analysis of data from patients with chronic HCV infection participating in a clinical trial of ledipasvir and sofosbuvir, SVR12 was associated with reduced fatigue, compared with baseline. High baseline serum levels of interferon-γ were associated with fatigue. Reductions in levels of chemokine (C-C motif) ligand 2 were associated with persistent fatigue after SVR12. Central and peripheral fatigue each associated with different biomarkers, suggesting different pathogenic pathways.
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
authors.forename: Lynn
authors.initials: L
authors.lastname: Gerber
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Estep
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: Carey
authors.initials: C
authors.lastname: Escheik
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
authors.forename: Ali
authors.initials: A
authors.lastname: Weinstein
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005221:Fatigue / Q000453:epidemiology*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D015415:Biomarkers; D016207:Cytokines; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: Fatigue; HCV; IL10; PDGF; TNF