Are parenchymal changes in early post-transplant biopsies related to preservation-reperfusion injury or rejection?
BACKGROUND
The progression of parenchymal changes in liver allograft biopsies due to preservation-reperfusion injury (PRI) and their differentiation from rejection related changes is poorly understood. The aim of this study was to determine which changes in a 1-week posttransplant biopsy could be attributed to PRI and which to acute rejection.


METHODS
One week protocol liver transplant biopsies from patients with mild PRI (day 1 AST<400 IU/L) were compared with those from patients with severe PRI (day 1 AST>2000 IU/L). Parenchymal changes (cholestasis, ballooning, steatosis, necrosis) and rejection-related inflammatory features (portal tract inflammation, bile duct inflammation, portal vein endothelial inflammation, hepatic vein endothelial inflammation, and centrilobular inflammation) were blindly assessed semiquantitatively.


RESULTS
Fat, cholestasis, and hepatocyte ballooning were significantly worse in the severe PRI group, and these features showed no correlation with histological features related to acute rejection. Centrilobular hepatocyte necrosis correlated with hepatic venular endothelial inflammation and centrilobular inflammation but not with rejection related features in portal tracts or with PRI. These findings suggest that centrilobular necrosis is a manifestation of a rejection-related parenchymal injury and may involve different pathogenetic mechanisms to rejection-related features in portal tracts.


CONCLUSIONS
This study indicates that in early posttransplant biopsies, fat, cholestasis, and ballooning can largely be attributed to PRI. By contrast, centrilobular hepatocyte loss should be suspected as a rejection related phenomenon, even if typical portal tract changes are not prominent, and augmentation of immunosuppression should be considered.
Neil
D A
DA
Department of Pathology, Medical School, University of Birmingham, Edgbaston, Birmingham, UK. d.neil@bham.ac.uk.
Hubscher
S G
SG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002779:Cholestasis / Q000473:pathology; D015925:Cryopreservation; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011309:Preservation, Biological / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000473:pathology*