Fatigue in Primary Biliary Cirrhosis: Prevalence, Pathogenesis and Management

Abstract

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.

Fatigue and its associated factors in liver transplant recipients in Beijing: a cross-sectional study

“…Another complication in cirrhosis, hepatic encephalopathy, may be another reason for patients' fatigue, for it is related to anaemia and fat-free mass depletion 10. Many studies found that fatigue among patients with end-stage liver diseases was associated with their depression, autonomic dysfunction and sleep disturbance 11 12…”

Early Primary Biliary Cholangitis is Characterised by Brain Abnormalities on Cerebral Magnetic Resonance Imaging

“…The finding of normal 1 H MRS in this cohort of PBC patients, of whom more than 50% reported symptoms of moderate or severe fatigue, is interesting. 1 H MRS has been found to be abnormal in patients with impaired quality of life attributed to liver disease. In patients with cirrhosis and hepatic encephalopathy, reduced basal ganglia choline/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) ratios have been widely reported.…”

“…Fatigue is a significant problem in patients with PBC, and although partly peripheral in origin, there appears to be a central component associated with sleep disturbance and autonomic dysfunction. [1][2][3][4] Patients with PBC also describe subtle cognitive impairment (particularly relating to concentration and memory) which can lead to significant functional impairment, 5 a phenomenon that has been associated with defective central corticotropin-releasing hormone neurotransmission and TReg inhibition in cholestatic animal models. 6,7 Central fatigue and cognitive impairment in PBC remain unresponsive to any form of current drug treatment.…”

Translation and validation of the Serbian primary biliary cholangitis-40 questionnaire

“…In keeping with its autoimmune origin, PBC primarily effects women and is associated with a significantly higher symptom burden than other chronic liver diseases (CLD), consequently negatively impacting patient’s HRQOL [3, 4]. Progressing slowly, the most common symptoms are dilapidating fatigue, itch and cognitive impairment which may occur at any point, independent of the histological stage of the disease [4, 5]. …”