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

Abstract

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. Methods: 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. Results: 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. Conclusions: 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.