Understanding Fatigue in Primary Biliary Cholangitis

Background: Fatigue affects 50% of primary biliary cholangitis patients and is severe in approximately 20%, significantly affecting quality of life. The pathogenesis of fatigue in primary biliary cholangitis is poorly understood. This study aimed to explore subgroups of fatigue to support targeting of selected groups in future clinical trials.

Methods: Data were derived from the UK-PBC cohort. Participants completed the PBC-40, Hospital Anxiety and Depression Score, Epworth Sleepiness Scale, and Orthostatic Grading Scale for symptoms assessment. Fatigue and cognitive symptoms were regarded as clinically significant if they exceeded the previously defined cutoff for "moderate" symptom.

Results: Of 2002, patients for whom full PBC-40, fatigue, and cognitive symptom domain scores were available, 1203 (60%) had significant fatigue and 730 (36%) had significant cognitive symptoms. Among the 1203 patients with significant fatigue, 663 (55%) also had significant cognitive symptoms (termed fatigue with cognitive symptoms) with a significant linear association between the fatigue and cognitive symptom severity. "Fatigue with cognitive symptoms" patients were younger and more likely to have severe fatigue. They also experienced greater social and emotional impact.

Conclusions: Fatigue in PBC is complex, and there has been no progress to date in identifying therapies able to improve it. One factor in slow progress may be the heterogeneity of patients describing fatigue complicating effective cohort selection for clinical trials. This study has identified potential discrete subgroups of fatigued patients with and without cognitive symptoms. The group of patients expressing "fatigue with cognitive symptoms" was homogenous and may represent a coherent cohort for clinical trials.

Keywords: Cholestasis; Cognitive impairment; Fatigue; Primary biliary cholangitis.