How can liver toxins be removed? Filtration and adsorption with the Prometheus system

The application of extracorporeal blood circuits in liver failure therapy has its roots in the two functions of the liver, first as a detoxifying and second as a synthetizing organ. In contrast to hydrophilic uremic toxins, most liver toxins are hydrophobic and bind preferentially to blood proteins. Consequently, the majority of these compounds cannot be removed by hemodialysis or similar dialytic procedures. Current systems use albumin as a transport vehicle for hydrophobic compounds across high flux membranes (e.g. albumin-dialysis, molecular adsorbent recirculating system (MARS)). In contrast to these devices, the Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) applies filtration across highly permeable membranes with a molecular weight cut-off of >300.000. These membranes facilitate a direct filtration of most of the toxin-bearing proteins. In a secondary circuit these toxins are then removed by adsorber beads assembled in specially designed cartridges. The protein-containing toxin-free solution returns to the primary circuit. Clinical testing of the Prometheus system's safety and efficacy parameters showed that cell counts and coagulation factors were not significantly affected. Total bilirubin-, bile acid- and plasma ammonia-levels were reduced in vivo by -21%, -43% and -40%, respectively. First successful therapeutic results have been obtained for patients treated for drug abuse and for patients waiting for transplantation. Thus, a combination of plasma fractionation with highly permeable membranes followed by a secondary circuit with adsorber cartridges proves to be the most effective method of removing toxic waste in liver failure. Further investigations will follow in order to extend the application of the Prometheus system to larger cohorts of patients.