Fatigue and circadian rhythm in non-cirrhotic primary biliary cholangitis: An exploratory comparison with primary sclerosing cholangitis and healthy controls

In non-cirrhotic primary biliary cholangitis, fatigue burden is similar to healthy controls and primary sclerosing cholangitis, but its phenotype is predominantly muscular (approximately 69%), independent of sex, age-adjusted employment, or routine disease metrics; daytime sleepiness and sleep duration are low/normal, and chronotype clusters in the intermediate range, with age - not disease - driving greater morningness. Primary sclerosing cholangitis shows a similar (weaker) direction of effect. These findings support routine fatigue phenotyping and muscle-focused interventions over cholestasis-directed therapies, and argue for objective endpoints (e.g., 31phosphorus magnetic resonance spectroscopy, actigraphy) in future trials.