Both peripherally acting pruritogens and central nervous dysfunction have been implicated in the pathogenesis of cholestatic pruritus [9] . According to these two concepts, most therapeutic interventions currently under study for cholestatic pruritus are either directed towards elimination of so far undefined pruritogens or modulation of central neurotransmission. The pharmaceutic options currently recommended include [29] : (1) anion exchange resins, such as cholestyramine and colestipol, which bind anions and amphipathic molecules and reduce their intestinal absorption and systemic accumulation. Despite extensive clinical experience, suggesting a beneficial effect in up to 90% of patients, no large clinical trials have evaluated the efficacy of exchange resins [298] . In patients lacking adequate improvement, treatment with (2) rifampicin may be helpful [298] [299] [300] [301] . Rifampicin is a semisynthetic antibiotic and as a potent pregnane X receptor (PXR) agonist leads to the induction of hepatic microsomal enzymes. Thereby, it may promote metabolism of potential pruritogens. As a thirdline option, (3) opioid antagonists (naloxone, nalmefene, naltrexone) have been found to reduce itch severity in patients with PBC [298, [302] [303] [304] . (4) The selective serotonin reuptake inhibitor sertraline [305, 306] has been reported to improve cholestatic pruritus in small clinical trials and has most recently been considered as a fourth-line treatment option [29, 280] . Other experimental approaches include 5-hydroxytryptamine receptor type 3 antagonists, cannabinoids, subhypnotic doses of propofol, plasmapheresis, albumin dialysis, and nasobiliary drainage in desperate cases, although adequate trials are lacking [29, 63] . Liver transplantation should be considered in serious cases in which all other strategies have failed, even if liver function is still conserved [29] .