Fatigue is a common debilitating complication of
primary biliary cirrhosis (PBC), the pathophysiologic mechanism of which is poorly understood. Recently, the
neuroactive steroid dehydroepinadrosterone
sulfate (DHEAS) was reported to be implicated in
Chronic Fatigue Syndrome in the absence of
liver disease. The present study was undertaken to analyse
fatigue scores and their relationship with disease severity and circulating levels of DHEAS as well as its precursors
DHEA and
pregnenolone in PBC patients with (n=15) or without
fatigue (n=10) compared to control subjects (n=11).
Fatigue was assessed using the
fatigue impact scale (FIS) including cognitive, physical and psychosocial subclasses.
Steroids were measured by radioimmunoassay or gas chromatography/mass spectrometry. Plasma concentrations of DHEAS were significantly reduced in PBC patients with
fatigue as compared to controls, while those of its precursors
DHEA and
pregnenolone remained within the control range. Plasma levels of DHEAS in PBC patients were significantly correlated with
fatigue severity as reflected by total FIS scores including total (rp=-0.42; p=0.018), as well as the cognitive (rp=-0.37; p=0.03), physical (rp=-0.48; p=0.006) and psychosocial (rp=-0.35; p=0.04) subclasses of
fatigue scores. No correlation of
fatigue scores was observed with indices of liver function. These findings suggest that reduced levels of the
neurosteroid DHEAS may contribute to
fatigue in patients with PBC; substitutive
therapy using DHEAS or its precursor
DHEA could be beneficial in the management of
fatigue in patients with low levels of DHEAS.