Nonsurgical Management of Fulmninant Hepatic Failure: Hepatocyte transplantation and bioartificial liver

Kim, Byung Ho

Abstract

BACKGROUND: Fulminant hepatic failure is a devastating process associated with high mortality, but no sequele after recovep. At the moment, there are no specific therapeutic modalities except for the orthotopic liver transplantation(OLT) which is limited to a small number of patients due to a lack of donor organ. Recently, several nonsurgical managements have been investigated to overcome the donor shortage and to bridge patients to OLT. These include artificial hepatic support systems, hepatocyte transplantation and extracorporeal liver support. Xenotransplantation is also being investigated to circumbent the donor shortage. Hepatocyte transplantation:The application of liver cell transplantation has been envisioned for temporary metabolic support during liver failure, provision of specific liver functions in inherited metabolic diseases of the liver and as a vehicle for ex vivo gene therapy. Potential advantages over OLT are that the procedure is simple, hepatoyctes can be cryopreserved for immediate use in need, the cost is less expensive and abrogation of allograft rejection may be easier by the modification of antigenicity during culture. Moreover, donor shortage can be overcome by the use of fetal hepatocytes, conditionally immortalized hepatocytes and possibly liver progenitor cells. However, the optimum route and the method are still being investigated. Recently, biodegradable matrix or cotransplantation with non-parencymal liver cells is used to improve and prolong the survival of transplanted hepatocytes in the peritoneum, and injection of donor type splenocytes into the thymus along with ablation of the peripheral lymphocytes with antilymphocyte globulin is adopted to tolerize the recipient to allogeneic hepatocytes. BioartiTicial liver:Presently, several bioartificial liver systems use mammalian hepatocytes held within cartridges, mostly hollow- fiber bioreactor perfused by plasma or whole blood. Plasma is separated from patient blood using Background:Fulminant hepatic failure is a devastating process associated with high mortality, but no sequele after recovep. At the moment, there are no specific therapeutic modalities except for the orthotopic liver transplantation(OLT) which is limited to a small number of patients due to a lack of donor organ. Recently, several nonsurgical managements have been investigated to overcome the donor shortage and to bridge patients to OLT. These include artificial hepatic support systems, hepatocyte transplantation and extracorporeal liver support. Xenotransplantation is also being investigated to circumbent the donor shortage. Hepatocyte transplantation:The application of liver cell transplantation has been envisioned for temporary metabolic support during liver failure, provision of specific liver functions in inherited metabolic diseases of the liver and as a vehicle for ex vivo gene therapy. Potential advantages over OLT are that the procedure is simple, hepatoyctes can be cryopreserved for immediate use in need, the cost is less expensive and abrogation of allograft rejection may be easier by the modification of antigenicity during culture. Moreover, donor shortage can be overcome by the use of fetal hepatocytes, conditionally immortalized hepatocytes and possibly liver progenitor cells. However, the optimum route and the method are still being investigated. Recently, biodegradable matrix or cotransplantation with non-parencymal liver cells is used to improve and prolong the survival of transplanted hepatocytes in the peritoneum, and injection of donor type splenocytes into the thymus along with ablation of the peripheral lymphocytes with antilymphocyte globulin is adopted to tolerize the recipient to allogeneic hepatocytes. BioartiTicial liver:Presently, several bioartificial liver systems use mammalian hepatocytes held within cartridges, mostly hollow- fiber bioreactor perfused by plasma or whole blood. Plasma is separated from patient blood using