During the course of the disease, up to 80% of PBC patients complain of chronic fatigue impairing quality of life and interfering with daily life activities [8, 59] . No correlation with the severity of the liver disease could be demonstrated [59] , but there is an association with autonomic dysfunction (in particular orthostatic hypotension) [60] , sleep disturbance and excessive daytime somnolence [60] , and, although weak, depression [61] , which might necessitate treatment for themselves. The exact pathophysiological mechanisms leading to chronic fatigue in PBC and other cholestatic diseases are not unraveled so far. Standard therapy of PBC with UDCA and even liver transplantation may fail to improve this often disabling symptom.