The Extent of Vacuolation in Non–Heart-Beating Porcine Donor Liver Grafts Prior To Transplantation Predicts Their Viability

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Livers exposed to prolonged warm ischemia (WI), such as those from non–heart-beating donors (NHBDs), are at higher risk of primary graft nonfunction (PNF). In a pig model of liver transplantation (LTx) from NHBDs, hepatocellular vacuolation, focal hepatocyte dropout, congestion, and sinusoidal dilatation appeared on biopsies taken after exposure to WI. In functioning grafts, vacuolation and sinusoidal dilatation were reversible after LTx, in contrast to PNF grafts. We studied whether the extent of these morphological signs and particularly vacuolation, present on pre-LTx biopsies, was associated with WI length and able to predict PNF, hepatocellular damage, and survival. Pre-LTx biopsies from pig livers exposed to incremental periods of WI were reviewed retrospectively. The extent of vacuolation was quantified blindly by a pathologist's semiquantitative score, validated by stereological point counting and digital image analysis, and then used to predict PNF and hepatocellular damage. On biopsies taken after WI, stereological point counting and digital analysis scoring contributed significantly in predicting PNF (P= 0.027 andP= 0.043, respectively) versus the pathologist's semiquantitative score (P= 0.058). Stereological point counting and digital image analysis predicted the extent of hepatocellular damage (P< 0.0001 andP= 0.001) versus the pathologist's semiquantitative score (P= 0.085). In conclusion, the extent of parenchymal vacuolation present on WI liver grafts reflects the severity of hepatocellular damage and predicts pig liver graft viability before LTx. Further studies are now warranted to evaluate whether these anoxic changes that are associated with liver graft viability in pigs also apply to human NHBD liver biopsies.

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