Intrahepatic complement activation, sinusoidal endothelial injury, and lactic acidosis are associated with initial poor function of the liver after transplantation.
BACKGROUND
Changes in glucose metabolism in the liver during transplantation have been recently described using microdialysis. Here, these findings are correlated with histopathologic, immunohistochemical, and ultrastructural changes in liver.


METHODS
Microdialysis catheters were inserted into 15 human livers, which were perfused with isotonic solution, and samples of perfusate were analyzed before harvest, after storage, and after reperfusion. At each stage Menghini needle biopsy samples were taken and each studied using light and electron microscopy.


RESULTS
Six livers showed serum biochemical evidence of initial poor function. These livers had significantly more staining for complement fragment 4d (C4d) of both lobular and periportal hepatocytes. C4d-positive hepatocytes were also found in the liver during cold storage (3 of 15). These periportal hepatocytes also showed evidence of necrosis and were found to have intracellular neutrophils. Hepatocyte rounding in zone III, necrosis, and C4d staining in recipient were also significantly correlated with the degree of lactic acidosis during this phase. Intrahepatic lactic acidosis at all time points was significantly associated with sinusoidal endothelial cell injury after reperfusion. There were no correlations between glucose, pyruvate, and glycerol levels and histopathologic changes in the liver.


CONCLUSIONS
In the patients studied, the degree of C4d staining correlated with initial poor function and was associated with intrahepatic lactic acidosis in the donor during cold storage and after reperfusion. Complement activity in the liver during cold storage may be after in situ activation. Intrahepatic lactic acidosis is associated with sinusoidal endothelial cell and hepatocyte injury. The role of intrahepatic neutrophils is uncertain and could possibly be in response to cell necrosis.
Silva
Michael A
MA
The Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham B15 2TH, United Kingdom.
Mirza
Darius F
DF
Murphy
Nick
N
Richards
Douglas A
DA
Reynolds
Gary M
GM
Wigmore
Stephen J
SJ
Neil
Desley A H
DA
D000140:Acidosis, Lactic / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D001706:Biopsy; D002102:Cadaver; D003167:Complement Activation; D005260:Female; D022781:Hepatocytes / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology*; D015427:Reperfusion Injury / Q000473:pathology; D014019:Tissue Donors; D016896:Treatment Outcome