Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyze fatigue in CHC and to determine its relationships with disease activity, resting energy expenditure (REE), circulating leptin, and TNF alpha.

Seventy-eight CHC patients, 22 healthy controls and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-a. All subjects completed the Fatigue Impact Scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients.

38 of the 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of the patients was significantly higher than that of the controls (53.2 +/- 40.1 vs. 17.7 +/- 16.9; p < 0.0001) and was more pronounced in females (p = 0.003). Leptin was increased significantly in CHC patients compared to controls (15.4 +/- 20.7 vs. 6.4 +/- 4.1 ng/mL; p < 0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r = 0.30, p = 0.01). This correlation increased when the physical domain of fatigue was concerned (r = 0.39, p = 0.0009). Furthermore, a similar positive correlation was found in PBC patients (r = 0.56, p = 0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load or the METAVIR score in CHC patients.

In summary, fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.