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 Galα1,3 Gal 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 Galα1,3 Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording.

Cytokine profiles in Tibetan macaques following α‐1,3‐galactosyltransferase‐knockout pig liver xenotransplantation

“…The increase in the ALT and AST levels after the first 12 hours suggested that serious liver damage had occurred at the early post‐Tx stage. The total rise in bilirubin was continuous until euthanasia, which is consistent with the findings of previous reports . The coagulation parameters were normal or near‐normal in our models.…”

Pig‐to‐baboon liver xenoperfusion utilizing GalTKO.hCD46 pigs and glycoprotein Ib blockade

“…Our findings of a disproportionate rise in the AST relative to the ALT in xenoperfusion experiments confirm results noted in other experiments [28]. The mechanisms underlying this phenomenon have yet to be elucidated.…”

Comparison of hematologic, biochemical, and coagulation parameters in α1,3‐galactosyltransferase gene‐knockout pigs, wild‐type pigs, and four primate species

“…In our recent experience in liver xenotransplantation (18), we observed that pig alanine transaminase (ALT), but not aspartate transaminase (AST), in GTKO pigs is significantly lower than in WT pigs, but similar to human and baboon levels (19). We hypothesized that there would be other differences in hematologic, biochemical, and coagulation parameters between WT and GTKO pigs.…”