Fatigue in primary sclerosing cholangitis is associated with sympathetic over-activity and increased cardiac output.

BACKGROUND & AIMS Patients with primary sclerosing cholangitis (PSC) frequently highlight the impact of fatigue on their life quality. The study aims were to evaluate fatigue and its associations in PSC and investigate whether overt autonomic dysfunction contributes to the expression of fatigue. METHODS All PSC patients under active follow-up at a regional liver centre were sent disease- and symptom-assessment tools. Three control groups were utilized; unselected community controls, patients with inflammatory bowel disease (IBD) without PSC, and cholestatic controls with primary biliary cirrhosis (PBC). A representative subgroup of PSC patients and normal controls underwent formal autonomic assessment. RESULTS Symptom-assessment tools were returned by 40 non-transplanted patients. PSC patients had significantly worse fatigue than population controls (P = 0.005). Fatigue was significant compared to population controls whether or not patients had accompanying IBD, although was more marked in those with both PSC and IBD. In patients with PSC and IBD, fatigue severity and autonomic symptoms were significantly increased in those with prior significant surgical intervention. Clinically significant autonomic dysfunction was seen in 22.5% of PSC patients, and of those, 78% had significant fatigue. Neurally mediated hypotension was found in 60% of PSC patients compared to 8% in the control group. The PSC group had increased sympathetic activity and reduced parasympathetic activity. CONCLUSION Fatigue is a significant problem in a minority of PSC patients and appears to be associated with autonomic dysfunction. Fatigued PSC patients should be screened for autonomic dysfunction and targeting such dysfunction represents a potential approach to treatment which warrants further exploration.