PBC is more frequently associated with pruritus than other chronic cholestatic liver diseases. During the course of the disease, pruritus occurs in 20% to 70% of patients and can often be the most distressing symptom [62] . It develops independently of the degree of cholestasis and the stage of disease. Its pathogenesis remains poorly understood and the potential pruritogens in cholestasis are undefined. The therapeutic efficacy of anion exchange resins like cholestyramine, the pregnane X receptor agonist, rifampicin, plasmapheresis, and albumin dialysis as well as nasobiliary drainage led to the conclusion that in cholestasis putative pruritogens accumulate in the circulation, are secreted into bile, and undergo an enterohepatic cycle. Itch could then be induced locally in the skin or in neuronal structures. Bile salt metabolites, progesterone metabolites, histamine, and endogenous opioids, among others, have all been proposed as causative agents. However, evidence for a key role of any of these suggested pruritogens in cholestasis is weak [63] .