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

Mar 11, 2026World journal of hepatology

Fatigue and daily body clock patterns in primary biliary cholangitis without cirrhosis compared to primary sclerosing cholangitis and healthy people

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Abstract

Among 152 enrolled individuals, muscular fatigue predominated in primary biliary cholangitis (PBC) compared to healthy controls.

Global fatigue scores did not differ significantly across primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and healthy controls (HC).
Muscular fatigue was more common in PBC and PSC, while HC reported mental fatigue more often.
Older age was associated with increased odds of muscular fatigue in PBC (odds ratio = 1.04 per year).
Daytime sleepiness levels were low and similar across all groups.
Chronotype, measured by the Morningness-Eveningness Questionnaire, was predominantly intermediate, with age being a factor in greater morningness.

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BACKGROUND: Fatigue is common and debilitating in primary biliary cholangitis (PBC) without clear relation to disease stage; mechanisms remain unclear. Circadian disruption is reported in end-stage liver disease, but evidence in non-cirrhotic PBC, and links to fatigue, is scarce.

AIM: To investigate the severity and phenotype of fatigue, daytime sleepiness, and chronotype in non-cirrhotic PBC, and compare findings with matched healthy controls (HC) and non-cirrhotic primary sclerosing cholangitis (PSC).

METHODS: Participants completed the Fatigue Impact Scale, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire Self-Assessment. Demographics, sleep habits, employment, and fatigue subtype (mentalmuscular) were recorded. In PBC/PSC, PBC-40 fatigue/itch domains and disease characteristics were analyzed. Group comparisons and multivariable models evaluated associations of fatigue phenotype and chronotype with demographic/disease variables. vs

RESULTS: We enrolled 152 individuals: 61 PBC, 30 PSC, and 61 HC. Global fatigue scores did not differ across groups. Muscular fatigue predominated in PBC/PSC, whereas HC more often reported mental fatigue; this pattern persisted after stratifying by employment and sex. In adjusted analyses, HC had lower odds of muscular fatigue than PBC [odd ratio (OR) = 0.30, 95% confidence interval (CI): 0.14-0.63;= 0.002]; PSC did not differ from PBC (OR = 1.25, 95%CI: 0.44-3.71;= 0.681). Older age independently increased the odds of muscular fatigue (OR = 1.04 per year, 95%CI: 1.01-1.07;= 0.016). Daytime sleepiness was low and similar between groups. Morningness-Eveningness Questionnaire Self-Assessment scores clustered in the intermediate range; age, not disease, predicted greater morningness. P P P

CONCLUSION: In non-cirrhotic PBC, fatigue shows a predominantly muscular phenotype independent of demographics/occupation and decoupled from conventional disease metrics. Chronotype and daytime alertness appear largely preserved, with age driving modest morningness. Findings support integrating fatigue phenotyping into assessment, prioritizing muscle-targeted interventions, and using carefully selected controls and objective endpoints in future studies.

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

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