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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 α-amanitine (0.1 mg/kg) and lipopolysaccharides (1 µg/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. [ABSTRACT FROM AUTHOR]

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 the plasma separator. This study was performed to demonstrate the safety and efficacy of this system. Hyperbilirubinemia was induced by ligating the bile duct in pigs, and 7 days later, only PE for 2 h (group PE) or PE for 2 h followed by PRD for 6 h (group PE + PRD) was performed. The separated plasma was recycled over anion-exchange resin through the extra fiber space of the plasma separator. The safety and efficacy of this system were evaluated based on the values of hemodynamic and laboratory parameters. Transfer from PE to PRD was completed in a few minutes. The hemodynamic status and blood cells counts were stable and hemolysis was not observed during the procedure. In the PE + PRD group, the concentrations of total bile acids continuously decreased (pretreatment, 155.5 ± 40.6 µM; 2 h [end of PE], 76.1 ± 14.4 µM; 8 h [end of PRD], 25.8 ± 9.1 µM) and the value was significantly lower than in the PE group after 6 h. The total bilirubin also continuously decreased during PRD (pretreatment, 55.3 ± 11.5 µM; 2 h [end of PE], 33.8 ± 8.4 µM; 8 h [end of PRD], 18.6 ± 7.7 µM) and was significantly lower than in the PE group after 4 h. No significant change was observed in other laboratory values. This PE-based PRD system allowed a swift transfer from PE to sorbent-based blood purification. The safety of this system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as a platform for artificial liver support. [ABSTRACT FROM AUTHOR]