Fatigue before, during and after antiviral therapy of chronic hepatitis C: results from the Virahep-C study

J Hepatol. 2012 Nov;57(5):946-52. doi: 10.1016/j.jhep.2012.06.030. Epub 2012 Jul 1.


Background & aims: Fatigue is the most frequent and often debilitating symptom of chronic hepatitis C. It is unclear whether successful therapy of hepatitis C leads to its clinical improvement. In the Virahep-C study, patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a and ribavirin for up to 48 weeks while undergoing assessment of viral kinetics and clinical symptoms.

Methods: Fatigue measurements were conducted, before, during and after therapy, as 'presence' (yes/no) and 'severity' (visual analog scale: 0-100mm). The clinical, histologic, and virologic features that correlated with the presence and degree of fatigue were assessed focusing upon changes associated with sustained virological response (SVR).

Results: At baseline, 52% (n=401) of participants reported having fatigue, which was more common in women than men (59% vs. 48%, p=0.02) and slightly more severe (30 vs. 22 mm, p=0.056). Fatigue was frequent and worse in cirrhotics versus those with lesser fibrosis (66% vs. 49%; 34 vs. 24 mm). Fatigue did not correlate with other parameters. The proportion of patients and median fatigue scores increased on treatment (52-78%; 25-40 mm, p<0.0001) with higher fatigue noted amongst those who ultimately achieved SVR (p<0.0001). On achieving SVR, there was a significant decrease in both frequency and severity of fatigue compared to their baseline (53-33%; 27-13 mm, both p<0.0001).

Conclusions: Fatigue is common in patients with chronic hepatitis C but is poorly associated with biochemical parameters. Sustained response is accompanied by substantial improvement of fatigue.

Trial registration: ClinicalTrials.gov NCT00038974.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Fatigue / epidemiology*
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Longitudinal Studies
  • Male
  • Polyethylene Glycols / therapeutic use*
  • Prevalence
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use*
  • Severity of Illness Index


  • Antiviral Agents
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00038974