Hepatocytes in the development of liver support systems

This thesis focuses on the development of alternative strategies in the treatment of patients with acute fulminant hepatic failure and inborn errors of metabolism, using hepatocytes as the basis of liver support. When compared with transplantation of the liver as an organ, the following theoretical advantages may be attributed to hepatocyte-based liver support systems: i) reduction of mortality, morbidity, and cost, due to less surgical trauma. ii) recovery of the patient's own liver is not precluded (acute hepatic failure)~ unnecessary removal of the own liver is not mandatory (inborn errors), iii) increased efficiency in use of donor organs by possibility of storage, and iv) possibility of genetransfer. As will be discussed, acute liver failure may be best served by extracorporeal systems as a means of providing temporary support while waiting for either spontaneous regeneration to occur, or a suitable donor liver to become available for transplantation. By such a strategy of buying time, liver transplantation might be avoided altogether in those patients with acute liver failure in whom the liver regenerates (13,80). In contrast, inborn errors of liver metabolism may be treated most efficiently by means of hepatocyte transplantation (implantable systems), combined with gene-therapy procedures, aimed at pennanently restoring the defunct enzymatic pathway. This is particularly true in those cases in which no other associated. liver impairment has yet developed (38).

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