Porcine alanine transaminase after liver allo-and xenotransplantation

Abstract

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording.

Fig. 1

(A) Mean AST values in different models of allo- and xenotransplantation. WT-WT Pig Allo w or w/o IS (WT-WT) = WT pig liver allotransplantion with or without immunosuppression. WT Pig-to-Baboon Xeno w/o IS (WT-Bab) = WT pig-to-baboon liver xenotransplantation without immunosuppression. GE Pig-to-Baboon Xeno w IS (GE-Bab) = genetically engineered (CD55, GTKO, GTKO/CD46) pig-to-baboon liver xenotransplantation with immunosuppression. Baboon-to-Baboon Allo w IS (Bab-Bab) = baboon-to-baboon liver allotransplantation with immunosuppression. Time-point “0” in the x-axis of the graph indicates pre-transplant data. Numbers underneath the time-points after transplantation indicate total number of transplants for each group. (P-values were calculated between groups WT-WT and GE-Bab.) Other groups WT-Bab and Bab-Bab were not included in statistical Student’s t-test calculation owing to the single transplant in each group. *P < 0.01. Data are presented as mean ± SD. Significance of the difference between two groups was determined by paired, two-tailed Student’s t-test using GraphPad Prism version 5 (GraphPad Software, San Diego, CA, USA). Values of P < 0.05 were considered significant. (B) Mean ALT values in different models of allo- and xenotransplantation. Time-point “0” in the x-axis of the graph indicates pre-transplant data. Numbers underneath the time-points after transplantation indicate total number of transplants for each group. (P-values were calculated between groups WT-WT and GE-Bab.) Other groups WT-Bab and Bab-Bab were not included in statistical Student’s t-test calculation owing to the single transplant in each group. *P < 0.01. (Other abbreviations as for A).