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

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: 0-100 mm). 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.