Amino acid and lipid profiles following pig-to-primate liver xenotransplantation.

As outcomes in clinical liver transplantation steadily improve, demand continues to exceed supply, leading to a substantial disparity in organ availability. The translation of porcine liver xenotransplantation (LXT) into a clinical reality aims to address this dilemma. Our laboratory has previously established an applicable model of α-1,3-galactosyltransferase knockout (GalT-KO) pig-to-primate LXT with continuous human coagulation factor infusion and costimulation blockade. This report aims to further investigate the post-LXT lipid and amino acid metabolism profile in our longest surviving recipients (25 and 29 days). Experimental samples and control samples, consisting of pre-transplant porcine and baboon serum and plasma, were analyzed for standard lipid profiles and for amino acid levels. Lipid profiles of LXT recipients remained stable following xenotransplantation compared to donor porcine baseline levels. Amino acid concentrations also remained similar to baseline controls, with the exception of a 3-fold increase in l-ornithine and more than a 10-fold decrease in l-arginine post-transplant when compared to both porcine and baboon baseline levels. The observed changes in l-arginine are consistent with prior studies investigating the effects of graft preservation injury following liver transplantation. These results indicate that the porcine liver can maintain most biochemical profiles stably post-operatively in baboons and suggest that arginine supplementation post-LXT may potentially be useful for further prolongation of xenograft survival.

Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation.

PURPOSE: To identify factors associated with removal from the liver transplantation waitlist because of death, deterioration of condition, or exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with emphasis on the role of locoregional therapy (LRT), defined as percutaneous thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy. MATERIALS AND METHODS: All patients listed for liver transplant at a single institution with exception points for HCC during 2004-2012 were evaluated. The most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one percent (125/177) of patients underwent liver transplantation, and 83% (147/177) underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver transplantation, 31 (60%) of livers were removed because of progression of HCC. RESULTS: The likelihood of transplant was higher for patients who received LRT (odds ratio [OR], 2.9; confidence interval [CI], 2.2-7.2) and lower for patients with multifocal tumors (OR, 0.25; CI, 0.12-0.52) and with larger tumors (OR, 0.94; CI, 0.90-0.98). Time on the waitlist (OR, 0.99; CI, 0.99-1.0) was not found to correlate with removal. LRT increased the likelihood of liver transplantation, specifically for patients with prolonged wait times. Patients who demonstrated complete response (CR) to LRT on the first follow-up imaging study were more likely to undergo liver transplantation. CONCLUSIONS: LRT increased the likelihood of a patient with HCC achieving liver transplant, particularly in patients facing prolonged waiting times. CR after LRT significantly increased the likelihood of liver transplantation.