Treatment of Fatigue in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis

  • Jennifer Y. Lee
  • Christopher J. Danford
  • Hirsh D. Trivedi
  • Elliot B. Tapper
  • Vilas R. Patwardhan
  • Alan BonderEmail author
Original Article


Background and Aims

Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions.


A comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class.


We identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69–1.08, p = 0.19, I2 = 56.2%). While liver transplantation did reduce degree of fatigue (SMD − 0.57, 95% CI − 0.89 to − 0.24, p = 0.001, I2 = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed.


While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.


Primary biliary cirrhosis Liver transplantation Ursodeoxycholic acid Weakness Malaise 


Compliance with ethical standards

Conflict of interest

No outside funding or grant support was involved in the production of this manuscript. The authors have no pertinent conflicts of interest.

Supplementary material

10620_2019_5457_MOESM1_ESM.docx (46 kb)
Supplementary material 1 (DOCX 45 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jennifer Y. Lee
    • 1
  • Christopher J. Danford
    • 2
  • Hirsh D. Trivedi
    • 2
  • Elliot B. Tapper
    • 4
  • Vilas R. Patwardhan
    • 3
  • Alan Bonder
    • 3
  1. 1.Department of MedicineBeth Israel Deaconess Medical CenterBostonUSA
  2. 2.Division of Gastroenterology and HepatologyBeth Israel Deaconess Medical CenterBostonUSA
  3. 3.Liver Center, Autoimmune and Cholestatic Liver Disease Program, Department of MedicineBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  4. 4.Division of Gastroenterology and Hepatology, University HospitalUniversity of MichiganAnn ArborUSA

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