HEPATOCYTE TRANSPLANTATION AS A BRIDGE TO ORTHOTOPIC LIVER-TRANSPLANTATION IN TERMINAL LIVER-FAILURE

The limited donor organ supply has led to several bridging techniques to sustain patients with acute and subacute liver failure, We report h ere the prospective, controlled trial of transplanted isolated fresh a nd cryopreserved human hepatocytes as a bridge to orthotopic liver tra nsplantation. Five hepatocyte transplant recipients with grade IV ence phalopathy and multisystem organ failure and four patients of equal il lness severity due to liver failure were studied, Medical therapy resu lted in a significant (P<0.05), but not normal, fall in blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver inju ry that did not improve cardiovascular or cerebral stability; this lea d to death within 3 days in all control patients, The five hepatocyte- treated patients maintained normal cerebral perfusion and cardiac stab ility, with withdrawal of medical support for 2 to 10 days before orth otopic liver transplantation. Biochemical evidence of liver injury imp roved significantly (P=0.004) and blood ammonia levels decreased signi ficantly (P=0.0005) to normal levels in the hepatocyte-treated patient s, Three of five patients who successfully bridged to whole liver allo graft transplant are alive, home, and normal with more than 20 months of follow-up, No infections or embolic or pulmonary complications resu lted from intra-arterial splenic hepatocyte infusion, Specific antipro tease production in a patients with genetically deficient alpha-1-anti trypsin disease, and immunohistochemical and electron microscopic evid ence of splenic ''hepatization'' are presented as evidence of the viab ility of hepatocyte splenic seeding, In conclusion, splenic transplant ation of differentiated adult hepatocytes can control hyperammonemia, correct genetic defects in liver function, and bridge life to orthotop ic liver transplantation in human liver failure.