The challenge of cholestatic pruritus

Pruritus can be the dominant symptom of cholestatic liver disease but is difficult to treat since unraveling its pathophysiology is a great challenge. Serum autotaxin activity correlates with pruritus intensity, but its causal relationship, expression pattern and exact mode of action during cholestasis remain to be established. The anion exchange resin cholestyramine, the PXR agonist rifampicin, the opioid antagonist naltrexone and the serotonine reuptake inhibitor sertraline are recommended by evidence-based guidelines as stepwise therapeutic approaches to treat itch in cholestasis. Rifampicin, the most effective antipruritic agent in cholestatic itch, has been shown to reduce autotaxin transcription in vitro. Experimental approaches include UVB phototherapy, extracorporeal albumin dialysis, nasobiliary drainage and in desperate cases even liver transplantation. Relevant clinical observations along with the different metabolic, neurologic and endocrine targets of available therapies in cholestatic pruritus are reviewed here.