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Published in: Digestive Diseases and Sciences 7/2021

01-07-2021 | Mood Disorders | Original Article

Understanding Fatigue in Primary Biliary Cholangitis

Authors: Naw April Phaw, Jessica Katharine Dyson, George Mells, David Jones

Published in: Digestive Diseases and Sciences | Issue 7/2021

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Abstract

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.
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Literature
1.
go back to reference Hirschfield GM, Beuers U, Corpechot C, et al. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–172.CrossRef Hirschfield GM, Beuers U, Corpechot C, et al. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–172.CrossRef
2.
go back to reference Goldblatt J, Taylor PJS, Lipman T, et al. The true impact of fatigue in primary biliary cirrhosis: a population study. Gastroenterology. 2002;122:1235–1241.CrossRef Goldblatt J, Taylor PJS, Lipman T, et al. The true impact of fatigue in primary biliary cirrhosis: a population study. Gastroenterology. 2002;122:1235–1241.CrossRef
3.
go back to reference Jopson L, Jones DEJ. Fatigue in primary biliary cirrhosis: prevalence, pathogenesis and management. Dig Dis. 2015;33:109–114.CrossRef Jopson L, Jones DEJ. Fatigue in primary biliary cirrhosis: prevalence, pathogenesis and management. Dig Dis. 2015;33:109–114.CrossRef
4.
go back to reference Mells GF, Pells G, Newton JL, et al. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58:273–283.CrossRef Mells GF, Pells G, Newton JL, et al. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58:273–283.CrossRef
5.
go back to reference Dyson J, Wilkinson N, Jopson L, et al. The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis. Aliment Pharmacol Ther. 2016;44:1039–1050.CrossRef Dyson J, Wilkinson N, Jopson L, et al. The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis. Aliment Pharmacol Ther. 2016;44:1039–1050.CrossRef
7.
go back to reference Jopson L, Khanna A, Howel D, et al. Rituximab is ineffective for treatment of fatigue in Primary Biliary Cholangitis. Hepatology. 2019;70(5):1646–1657.CrossRef Jopson L, Khanna A, Howel D, et al. Rituximab is ineffective for treatment of fatigue in Primary Biliary Cholangitis. Hepatology. 2019;70(5):1646–1657.CrossRef
8.
go back to reference Hollingsworth KG, Newton JL, Robinson L, et al. Loss of capacity to recover from acidosis in repeat exercise is strongly associated with fatigue in primary biliary cirrhosis. J Hepatol. 2010;53:155–161.CrossRef Hollingsworth KG, Newton JL, Robinson L, et al. Loss of capacity to recover from acidosis in repeat exercise is strongly associated with fatigue in primary biliary cirrhosis. J Hepatol. 2010;53:155–161.CrossRef
9.
go back to reference Grover VPB, Southern L, Dyson J, et al. Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging. Aliment Pharmacol Ther. 2016;44:936–945.CrossRef Grover VPB, Southern L, Dyson J, et al. Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging. Aliment Pharmacol Ther. 2016;44:936–945.CrossRef
10.
go back to reference Burak KW, Le T, Swain MG. Increased sensitivity to the locomotor-activating effects of corticotropin-releasing hormone in cholestatic rats. Gastroenterology. 2002;122:681–688.CrossRef Burak KW, Le T, Swain MG. Increased sensitivity to the locomotor-activating effects of corticotropin-releasing hormone in cholestatic rats. Gastroenterology. 2002;122:681–688.CrossRef
11.
go back to reference Kerfoot SM, D’Mello C, Nguyen H, et al. TNF secreting monocytes are recruited into the brain of cholestatic mice. J Hepatol. 2006;43(1):154–162.CrossRef Kerfoot SM, D’Mello C, Nguyen H, et al. TNF secreting monocytes are recruited into the brain of cholestatic mice. J Hepatol. 2006;43(1):154–162.CrossRef
12.
go back to reference Carbone M, Mells G, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144:560–569.CrossRef Carbone M, Mells G, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144:560–569.CrossRef
13.
go back to reference Jacoby A, Rannard A, Buck D, et al. Development, validation and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005;54:1622–1629.CrossRef Jacoby A, Rannard A, Buck D, et al. Development, validation and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005;54:1622–1629.CrossRef
14.
go back to reference Newton JL, Bhala N, Butt J, et al. Characterisation of the association and impact of symptoms in primary biliary cirrhosis using a disease specific quality of life measure. J Hepatol. 2006;44:776–782.CrossRef Newton JL, Bhala N, Butt J, et al. Characterisation of the association and impact of symptoms in primary biliary cirrhosis using a disease specific quality of life measure. J Hepatol. 2006;44:776–782.CrossRef
15.
go back to reference Newton JL, Hudson M, Phaedra T, et al. Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis. Hepatology. 2007;45:1496–1505.CrossRef Newton JL, Hudson M, Phaedra T, et al. Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis. Hepatology. 2007;45:1496–1505.CrossRef
16.
go back to reference Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxycholic acid and long term prognosis in primary biliary cirrhosis. Hepatology. 2008;48:871–877.CrossRef Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxycholic acid and long term prognosis in primary biliary cirrhosis. Hepatology. 2008;48:871–877.CrossRef
Metadata
Title
Understanding Fatigue in Primary Biliary Cholangitis
Authors
Naw April Phaw
Jessica Katharine Dyson
George Mells
David Jones
Publication date
01-07-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06502-0

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