Study of assisted liver transplantation for acute liver failure -Development of xeno auxiliary liver transplantation-

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We studied auxiliary heterotopic liver transplantation (ALT) in animals to develop a life support method for acute and subacute liver failure.An experimental study on a rat model of extrahepatic portal obstruction was firstly performed to evaluate non-invasive method of ICG clearance mater (RK 1,000). This tool was very useful, especially in small animals, for evaluation of liver function without sampling of peripheral blood.In the second part of this project, a simple ALT model was established in rats using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubine concentrations of Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained to the normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubine levels were not returned to the preoperative value of Gunn rats. There was a possibility that hepatic stem cells were included in ALT liver and generated to enzyme producing cells.Finally, xenogenic ALT was performed from mice or hamsters to rats. A difficulty was found in reconstration of biliary tract. The combination therapy of cyclosphamide plus FK-506 was effective for prolongation of the graft survival.