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

Abstract

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.

Published by Elsevier B.V.

Figures

Figure 1. `Presence of' and `severity' of fatigue at baseline, on treatment and follow-up of all patients

(a) Proportion (`yes/no') of patients with fatigue and, (b) the Severity of fatigue (VAS), at baseline, on treatment and on follow-up. Each point marks the week of patient evaluation and fatigue measurement: at screening visit 2, treatment weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44 and 48 (until week 24 for non-responders), and on follow-up at 4, 12 and 24 weeks after treatment discontinuation. ◻ All patients on treatment, ▵ Responder, ◯ Non-responders (NR). Solid line, on treatment; and dashed line: off-treatment follow-up weeks.

Figure 2. `Presence of' and `severity' of fatigue at baseline, on treatment and follow-up amongst those achieving SVR versus NR

(a) Proportion of patients with fatigue and (b) severity of fatigue amongst those who achieved sustained virologic response (SVR) versus NR. ▵ SVR (blue line), ◯ NR patients (red line). Solid line: on treatment, and dashed line: off-treatment, follow-up weeks.

Figure 3. Severity of fatigue categorized by baseline fatigue status in responders and NR

Severity of fatigue by baseline fatigue status in (a) Responders (b) NR patients. Red line: none-to-mild fatigue: VAS ≤10; Green line: moderate fatigue: VAS >10 to ≤40 and; Blue line: severe fatigue: VAS >40. (a) ▵ Responder, (b) ◯ Non-responders. Solid line: on treatment, and dashed line: off-treatment follow-up weeks.