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A Predictive Model for Fatigue and Its Etiologic Associations in Primary Biliary Cirrhosis

Lookup NU author(s): Professor Julia NewtonORCiD, Jessie Pairman, Katharine Wilton, Professor David Jones


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Background & Aims: Excessive day-time somnolence and autonomic dysfunction are biological processes prevalent in Primary Biliary Cirrhosis (PBC) that associate with fatigue. Here we explore how these biological associates inter-relate, and their cumulative impact upon typical clinical cohorts. Methods: A predictive model for daytime hypersomnolence (Epworth Sleepiness Scale (ESS)) and autonomic dysfunction (Orthostatic Grading Scale (OGS)) was developed in a derivation cohort (n=124) and subsequently validated in a second cohort (n=114). Subjects also completed the disease specific quality of life tool, the PBC-40. Results: A composite predictive criterion (presence of either ESS ≥10 or OGS ≥4) for the presence of fatigue in PBC patients had a sensitivity of 0.71 (95% confidence intervals 0.59-0.81) and specificity 0.8 (0.67-0.9) (positive predictive value (PV); 0.84 (0.72-0.92), negative PV; 0.66 (0.53-0.78) for moderate or severe fatigue). Ninety-seven percent of severely fatigued patients (0% of non-fatigued) met the aetiology predictive criterion (χ2 49.6, P<.0001). Expression of both significant daytime somnolence and autonomic dysfunction was not associated with more severe fatigue, suggesting that there is a threshold effect for fatigue in PBC. When applied to a second independent cohort, the composite criterion retained strongly significant predictive value for fatigue. Conclusions: A significant proportion of fatigue in PBC associates with one or both of autonomic dysfunction (OGS ≥4) and sleep disturbance (ESS ≥10). Those meeting both ESS and OGS criteria were not more severe fatigued than those meeting the diagnostic criterion for either OGS or ESS alone. A threshold effect for fatigue has implications for potential therapeutic interventions. © 2008 AGA Institute.

Publication metadata

Author(s): Newton JL, Pairman J, Sutcliffe K, Wilton K, Jones DEJ

Publication type: Article

Publication status: Published

Journal: Clinical Gastroenterology and Hepatology

Year: 2008

Volume: 6

Issue: 2

Pages: 228-233

ISSN (print): 1542-3565

ISSN (electronic): 1542-7714

Publisher: W.B. Saunders Co.


DOI: 10.1016/j.cgh.2007.11.021

PubMed id: 18237872


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Funder referenceFunder name
G0500020Medical Research Council