Porcine Model of Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure

Abstract

Auxiliary partial orthotopic liver transplantation (APOLT) has been an effective alternative in acute liver failure (ALF), but clinically several problems remain to be resolved. Thus, we attempt to establish an APOLT model for ALF using a large animal and demonstrate the validity of our model. In experiment 1, we created an animal model of ALF using pig. ALF was induced by resection of 70% of the whole liver under total hepatic vascular exclusion (THVE). The duration of ischemia was 90 minutes. In experiment 2, we tried to make an APOLT model by using this ALF model as a recipient. That is, during 90 minutes of THVE, 70% hepatectomy and subsequent partial orthotopic transplantation was completed. In experiment 1, six of seven pigs died within three days with jaundice and massive ascites. Based on microcirculatory disturbance of the remnant liver and hepatocellular necrosis, 70% hepatectomy with 90 minutes of THVE was considered a proper model of ALF. In experiment 2, six out of seven APOLT model animals survived more than four days. T. Bil levels in the APOLT model remained consistently within the normal range throughout the observation period. In immunohistochemistry, several labeled nuclei stained with Ki67 were identified in native liver of the APOLT model. This APOLT procedure provided temporary liver function support and enabled the recipient to survive until the failing native liver had regenerated. Our APOLT model could be suitable and useful for understanding the role of APOLT in ALF.