Liver support systems

Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity of toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile acids or mercaptans) are released into the systemic circulation, thus altering many enzymatic cellular processes. Patients frequently die while on the transplantation waiting list because of organ scarcity. Systems supporting liver function may be useful to avoid further complications due to the typical toxic state, 'bridging' the patients to the transplantation, or, in the event of an acute decompensation of a chronic liver disease, sustain liver function long enough to permit the organ's regeneration and functional recovery. An ideal liver support system should substitute the main functions of the liver (detoxification, synthesis and regulation). Extracorporeal systems now available may be totally artificial or bioartificial. While the first are only able to perform detoxification, the second may add the functions of synthesis (plasma proteins, coagulation factors) and regulation (neurotransmitters). Bioartificial liver working with isolated hepatocytes and a synthetic membrane in an extracorporeal system are however still far from being ready for clinical use. At present, liver insufficiency may be treated with an extracorporeal support technology aimed either at detoxification alone or at a real purification. Charcoal hemoperfusion or exchange/absorption resins may be used for blood detoxification. Blood or plasma exchange, from a theoretical point of view, could be suitable for a polyvalent intoxication, such as liver failure; however, the multicompartmental distribution of some solutes largely endangers the efficacy of these procedures. Selective plasmapheresis techniques are now available for some solutes (e.g. styrene for bilirubin) and may progressively reduce the plasma levels and presumably the deposits of the solute. Novel treatments introduced to improve detoxification, mainly of the protein-bound substances, are the molecular adsorbent recirculation system (MARS) and Prometheus systems. MARS performs an albumin dialysis, where albumin is the exogenous carrier for the toxic substances, and different experiences have proved its efficacy mainly in the treatment of hepatic encephalopathy, while data on survival are still limited to small case series. With Prometheus, the most recent system developed for a wide Liver Support Systems 397 detoxification, albumin-bound toxins are directly removed in two separate cartridges with different solute affinity, without the need for exogenous albumin; plasmadsorption is then coupled with a real dialysis process. After promising initial results, the efficacy of Prometheus in the patients' hard endpoints will be evaluated in a large international trial. On the whole, liver support systems may offer, in many cases, a survival benefit. Stem cells are however, even in this filed, the real great hope for the future of patients with end-stage liver disease.