Patients with primary biliary cirrhosis (PBC) frequently experience significant fatigue thought to result from as-yet-unidentified central nervous system (CNS)-mediated processes. Pilot studies have suggested that autonomic dysfunction is a frequent occurrence in PBC and may contribute to the pathogenesis of this fatigue. The degree to which autonomic dysfunction affects the PBC population as a whole, and its interrelationship with other symptoms experienced by PBC patients remains unstudied. In this study, we used a geographically defined, fully representative PBC patient cohort to study the prevalence of symptoms of autonomic dysfunction and its relationship with other symptoms of PBC. Symptoms of cardiovascular autonomic dysfunction (as assessed using the Orthostatic Grading Scale [OGS]) were significantly more frequently reported and significantly more severe in PBC patients than in both matched normal controls (40% versus 6% with moderate or worse orthostasis (P < .0001), mean OGS score 3.2 +/- 3.4 versus 1.3 +/- 1.9, P < .005) and in patients with primary sclerosing cholangitis and in severity were independently associated with severity of fatigue and cognitive symptoms (both r2 = 0.3, P < .0001). Thirteen of 20 patients with an OGS value > 4 (moderate severity and worse) had significant abnormality in autonomic regulation of blood pressure, which was identified on dynamic testing.
Conclusion: Symptoms suggestive of autonomic dysfunction frequently occur in PBC patients and reflect dysregulation of actual blood pressure. Autonomic dysfunction is independently associated with both fatigue and, importantly, symptoms of cognitive dysfunction, suggesting the potential for significant organic sequelae.