Plasma exchange-based plasma recycling dialysis system as an artificial liver support

We developed a plasma recycling dialysis (PRD) system based on plasma exchange (PE). In this system, rapid reduction of toxic substances and restitution of deficient essential substances are performed by PE and subsequent blood purification is performed by dialysis between separated plasma recycled over a purification device and the patient's blood across the membrane of a plasma separator. To demonstrate the safety and efficacy of this system, we used a pig model of fulminant hepatic failure (FHF) and anion exchange resin, activated charcoal and hemodialysis for the purification device. FHF was induced by intraportal administration of alpha-amanitine (0.1 mg/kg) and lipopolysaccharides (1 microg/kg) in pigs. Three groups of animals were studied: group 1, diseased controls (N = 4); group 2, PE group (N = 4), 16 h after drug infusion the pigs underwent PE of approximately 1.2 L for 2 h; and group 3, PE + PRD group (N = 4), the pigs underwent PE followed by PRD for 6 h. The hemodynamic status of all animals was stable during the procedure. In group 3, the values of ammonia, total bile acid and total bilirubin continuously decreased and were significantly lower than those of the animals in group 2 24 h after the induction of FHF. The Fischer ratio was significantly higher than in group 2 after 24 h. Group 3 pigs maintained a higher level of consciousness and survived longer than group 2 pigs. Safety of this PE-based PRD system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as an artificial liver support.