These authors have contributed equally to this article.
Gene Expression Profiling of Acute Liver Stress During Living Donor Liver Transplantation
Article first published online: 21 FEB 2006
American Journal of Transplantation
Volume 6, Issue 4, pages 806–824, April 2006
How to Cite
Borozan, I., Chen, L., Sun, J., Tannis, L. .-L., Guindi, M., Rotstein, O. D., Heathcote, J., Edwards, A. M., Grant, D. and McGilvray, I. D. (2006), Gene Expression Profiling of Acute Liver Stress During Living Donor Liver Transplantation. American Journal of Transplantation, 6: 806–824. doi: 10.1111/j.1600-6143.2006.01254.x
- Issue published online: 21 FEB 2006
- Article first published online: 21 FEB 2006
- Received 1 July 2005, revised 20 October 2005, revised 1 December 2005, accepted for publication 4 December 2005
- Gene expression profiling;
During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well-understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies were taken early in the donor operation (OPENING), after transection of the donor liver (PRECLAMP) and following implantation of the graft (post hepatic artery, [PHA]); these were evaluated for histology, tissue glutathione content and gene expression using a 19K-human cDNA microarray. LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (> or <2-fold, p < 0.01). By real-time PCR a subset of 25 genes was verified (15 increased, 10 decreased). These genes were similarly altered in another condition of acute liver stress (the response to braindeath), but not in three chronic liver disease states (HCV, HBV and PBC). This study has identified a set of genes whose expression is altered in acute, but not chronic, liver stress, likely to play a central role in the pathogenesis of acute liver injury of liver transplantation.