MARS: The ultimate warrior against pruritus of cholestasis?

Pruritus is the most prevalent symptom of cholestasis. Although it is often under-appreciated by physicians, pruritus is more than just an annoyance for patients with cholestasis. It reduces quality of life and can lead to significant disability. When very severe, it may sometimes cause the patient to even contemplate suicide. The pruritus of cholestasis is a difficult clinical problem to manage and current medical treatments accepted as conventional are unsatisfactory in a considerable proportion of cases, causing distress and exasperation to the patient as well as to the doctor [1]. Progress in the study of pruritus has been hampered by two major problems. One is the subjective and multi-dimensional nature of pruritus, which makes objective assessment difficult. The dimensions include: (1) a sensory signal (itch), (2) an emotional reaction (discomfort, stress) and (3) a behavioural response (scratching); the latter two components appear to be susceptible to great individual variability and the former cannot yet be measured. The other major problem is the poorly defined pathogenesis of pruritus in cholestasis. Peripherally acting pruritogens and altered central neurotransmission have been implicated as causing pruritus in cholestasis. Unfortunately, the pruritogen(s) are not yet identified although bile salts, progesterone metabolites, histamine, and endogenous opioids have been proposed to induce pruritus [2]. A new potential player in this field has recently emerged, namely lysophosphatidic acid (LPA) which is a potent neuronal activator and is formed from lysophosphatidylcholine by the enzyme autotoxin (ATX) [3]. Nevertheless, and as a consequence, current anti-pruritic treatments are mostly empirical and not consistently effective. Therapeutic efforts should always include an adequate therapy of the underlying hepatobiliary disease, as it may result in relief of pruritus. The specific treatment of pruritus can be categorized as (1) procedures aimed at the removal of pruritogens from the body, including non-absorbable anion-exchange resins which bind many hydrophobic substances in the intestinal lumen, and invasive procedures such as hemodialysis, plasmapheresis, extracorporeal albumin dialysis (mainly the molecular adsorbent recirculating system or MARS), nasobiliary drainage or even surgical partial biliary diversion; (2) drugs aimed at alter-