[What future for clinical xenograft of the liver?]

In the cyclosporine era liver orthotopic allotransplantation has shown to be very effective in the treatment of many end-stage liver diseases. Currently, the major limitation in clinical transplantation is the shortage of donor organs unlikely solvable by alternative policies or approaches such as living donors and artificial organs. Animals have been considered as an alternative source of organs offering the following advantages: availability of a predictable and ready supply of donor organs, opportunity to practice transplantation as an elective procedure, possibility to match the size of the graft recipient. However, immunologic barriers are thought to make xenotransplantation impractical between widely divergent (discordant) species. Hyperacute xenograft rejection, in fact, consists of an immediate, diffuse intravascular coagulopathy followed by an aggressive cellular reaction. Recipient preformed natural antibodies and complement are involved in the humoral phase of hyperacute rejection. The violence of this reaction depends on the titer of natural antibodies and on the divergency of the species involved. Species more closely related (concordant) exhibit a less aggressive reaction characterized by an acute cellular rejection. Hepatic allografts and xenografts, though, are unusually resistant to humoral injury and undergo a combination of both humoral and cellular rejection. Preliminary studies have demonstrated a prolonged reduction in natural antibodies accomplished by plasmapheresis and cyclophosphamide combined treatment. Furthermore, new therapeutic agents such as FK 506, rapamycin and deoxyspergualin may find widespread application in clinical transplantation. FK 506 has shown to possess a remarkable efficacy in reversing refractory hepatic allograft rejection as well as ability to inhibit humorally mediated immunity.(ABSTRACT TRUNCATED AT 250 WORDS)