Liver transplantation has progressed from an experimental procedure with a high mortality rate to an accepted clinical procedure with nearly 70% survival for one year. The indications for this radical and expensive, though often life-saving procedure, are not specific and remain largely a subjective decision. A recently described defect in severe liver disease is a reduced ability of the diseased liver to convert phenylalanine to tyrosine and methionine to cyst(e)ine which become manifest only after feeding a tyrosine and cyst(e)ine-free diet for several weeks. The hepatic inability to synthesize these normally dietary dispensible amino acids may extend to other compounds of great importance such as carnitine and choline of the transmethylation and taurine of the transsulfuration pathway of methionine. Kinetic techniques have been developed to measure the conversion of phenylalanine to tyrosine, as well as estimate amino acid appearance and oxidation rate and albumin synthesis, and can be developed for methionine metabolism. Alterations in these dynamic processes may reflect end-stage liver disease and the need for orthotopic liver transplantation better than conventional methods as well as be used to monitor the clinical course post-transplantation. The intent of this study will be to apply tracer technology to these problems in human orthotopic liver transplantation as well as in animal models of liver disease. The ultimate goal will be to develop more sensitive assays of liver function as well as determine the effect of liver dysfunction on aromatic and sulphur amino acid metabolism.
| Palombo, J D; Pomposelli, J J; Hirschberg, Y et al. (1989) Glycolytic support of adenine nucleotides in rat liver flush-preserved with UW or Collins' II. Importance of donor nutritional status. Transplantation 48:901-5 |
| Driscoll, D F; Pinson, C W; Jenkins, R L et al. (1989) Potential protective effects of furosemide against early renal injury in liver transplant patients receiving cyclosporine-A. Crit Care Med 17:1341-3 |
