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Biomarkers of Early Liver Graft Damage in Circulatory Death and Brain Death Donors: A Propensity Score Matching
Víctor Lopez-Lopez1, Carlos Martínez-Caceres2, David Ferreras1
1Department of Surgery, Virgen de la Arrixaca University Hospital, Biomedical Research Institute of Murcia-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Insights
Donation after circulatory death (DCD) liver grafts show similar initial damage markers to donation after brain death (DBD) grafts. Complications may arise from later events, not initial warm ischemia time in DCD liver transplantation.
Area of Science:
- Hepatology and Transplant Surgery
- Immunology and Pathology
Background:
- Donation after circulatory death (DCD) liver grafts are associated with warm ischemia time and increased complications compared to donation after brain death (DBD) grafts.
- Understanding the biological differences in DCD vs. DBD liver grafts is crucial for improving transplant outcomes.
Purpose of the Study:
- To compare histologic and biological markers of initial liver damage between DCD and DBD liver grafts.
- To investigate the relationship between specific biomarkers and clinical factors in liver transplantation.
Main Methods:
- Retrospective analysis of biopsy samples from DCD and DBD liver grafts (November 2014 - December 2018).
- Evaluation of immunohistochemical markers including apoptosis (p21), senescence (TERT), cell damage (caspase-3), endothelial damage (VEGF), stem cells (CD90), hypoxia (HIF1A), inflammation (COX-2), and rejection (CD44).
- Propensity score matching (PSM) to control for confounding variables between DCD and DBD groups.
Main Results:
- Positive expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, CD90) was observed, with no significant differences between DCD and DBD grafts regarding ischemic cholangiopathy.
- Post-PSM analysis revealed significant associations between CD90 and male donors, TERT and donor sodium levels, HIF1A and steatosis, and CD44 and donor vasoactive drugs/AST levels.
Conclusions:
- Initial liver damage in DCD grafts, assessed by immunohistochemistry, is comparable to DBD grafts.
- The increased complications and cholangiopathy in DCD liver transplantation may be attributed to post-transplant phenomena rather than initial warm ischemia-related damage.
Background:
Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]).
Methods:
This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage-related warm ischemia time.
Results:
Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03).
Conclusions:
DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.
