Transplantation 1997 Feb 27;63(4):559-69

Hepatocyte transplantation as a bridge to orthotopic liver transplantation i
terminal liver failure
 
Strom SC, Fisher RA, Thompson MT, Sanyal AJ, Cole PE, Ham JM, Posner MP
Department of Surgery, Medical College of Virginia, Richmond 23298, USA

Abstract
The limited donor organ supply has led to several bridging techniques to sustain
patients with acute and subacute liver failure. We report here the prospective,
controlled trial of transplanted isolated fresh and cryopreserved human
hepatocytes as a bridge to orthotopic liver transplantation. Five hepatocyte
transplant recipients with grade IV encephalopathy and multisystem organ failure
and four patients of equal illness severity due to liver failure were studied.
Medical therapy resulted in a significant (P<0.05), but not normal, fall in
blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver
injury that did not improve cardiovascular or cerebral stability; this lead to
death within 3 days in all control patients. The five hepatocyte-treated
patients maintained normal cerebral perfusion and cardiac stability, with
withdrawal of medical support for 2 to 10 days before orthotopic liver
transplantation. Biochemical evidence of liver injury improved significantly
(P=0.004) and blood ammonia levels decreased significantly (P=0.0005) to normal
levels in the hepatocyte-treated patients. Three of five patients who
successfully bridged to whole liver allograft transplant are alive, home, and
normal with more than 20 months of follow-up. No infections or embolic or
pulmonary complications resulted from intra-arterial splenic hepatocyte
infusion. Specific antiprotease production in a patients with genetically
deficient alpha-1-antitrypsin disease, and immunohistochemical and electron
microscopic evidence of splenic "hepatization" are presented as evidence of the
viability of hepatocyte splenic seeding. In conclusion, splenic transplantation
of differentiated adult hepatocytes can control hyper-ammonemia, correct genetic
defects in liver function, and bridge life to orthotopic liver transplantation
in human liver failure