Fatigue in Primary Biliary Cirrhosis: Prevalence, Pathogenesis and Management

Fatigue is a significant problem in approximately 50% of primary biliary cirrhosis (PBC) patients, with 20% of all patients experiencing significant or life-altering fatigue. Large-scale population studies show that fatigue has a major impact on quality of life (QoL) in PBC, and that it disproportionately affects younger patients. The presence of social dysfunction that accompanies fatigue appears to be a major factor in determining whether fatigue of a particular severity impacts on QoL. The pathogenesis of fatigue in PBC remains unclear, although it is unrelated to the severity of underlying disease and is unresponsive to ursodeoxycholic acid. Perhaps, unsurprisingly, it appears to be complex in origin, probably multifactorial in the majority of patients and associated with depression, autonomic dysfunction and sleep disturbance. Clinically, fatigue has both central and peripheral components. The central component is associated with cognitive impairment and sleep disturbance and characterised by neurophysiological abnormalities of activation and facilitation, together with CNS changes. Peripheral fatigue is associated with muscle dysfunction and an inability to sustain exercise. One hypothesis is that the central processes result directly from cholestasis, which impacts autonomic centres in the brain; these processes then regulate peripheral muscle perfusion, leading to systemic peripheral effects. At present, there is no specific drug therapy for fatigue in PBC and no significant improvement following transplantation. In managing patients with fatigue, understanding their situation is crucial and advice regarding pacing and maintaining social interactions is critical. Most important of all is an understanding of the impact this symptom has on patients' lives and an empathetic clinical interaction. (C) 2015 S. Karger AG, Basel