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

Background and AimsFatigue 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.MethodsA 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.ResultsWe 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, I-2=56.2%). While liver transplantation did reduce degree of fatigue (SMD -0.57, 95% CI -0.89 to -0.24, p=0.001, I-2=67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed.ConclusionsWhile 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.