Efficacy of Double Filtration Plasmapheretic Cross Circulation with a High Permeability Membrane using Whole Liver on Porcine Fulminant Hepatic Failure Model

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In the use of bioartificial liver devices, preparation of sufficient liver cell mass to provide adequate metabolic support, reduction of xenogeneic immune reaction, and avoidance of viral transmission are required. We developed a plasmapheresis using semipermeable membrane combined with whole liver perfusion (PMWLP) system, which offered a large number of functional liver cells, an immunoprotection, and a barrier to the viral transmission. The effect of the PMWLP system in porcine FHF model was investigated. Porcine FHF model was established by the intraportal administration of alpha-amanitin and lipopolysaccharide. Nine hours after the drugs injection, the FHF pigs were connected to the PMWLP system for 6 hours (n=5). In control pigs (n=10), the circuit was not connected to the porcine whole liver. Animal survival was significantly longer in the PMWLP treated pigs. Although the control pigs developed hypotension progressively, the PMWLP treated pigs demonstrated a cardiovascular stabilization. The PMWLP treatment significantly suppressed the elevation of liver enzymes, total bile acid, ammonia, and metionine. The degrees of hepatocyte necrosis and neutrophil infiltration were remarkably lessened in the PMWLP treated pigs. The PMWLP system prolonged animal survival, prevented cardiovascular instability, attenuated liver injury, enhanced bile acid metabolism, and decreased the hepatic encephalopathy related agents.