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Updated: Apr 12, 2026
Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment
Published on: May 10, 2022
The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non
Shirin Elizabeth Khorsandi1, Alberto Quaglia1, Siamak Salehi1
1Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Abstract:
Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.
Insights
MicroRNA (miRNA) analysis showed limited potential for distinguishing the quality of livers from donation after cardiac death (DCD) based on clinical outcomes. Further research is needed to identify reliable biomarkers for DCD liver transplant success.
Area of Science:
- Transplantation immunology
- Molecular biology
- Biomarker discovery
Background:
- Donation after cardiac death (DCD) livers are considered marginal organs for transplantation.
- The utilization of DCD livers is associated with an increased risk of primary non-function (PNF) or early graft dysfunction (EGD).
- Identifying biomarkers to predict DCD liver quality is crucial for improving transplant outcomes.
Purpose of the Study:
- To investigate the potential of microRNA (miRNA) expression profiles in discriminating between DCD livers with varying clinical outcomes.
- To assess whether specific miRNA signatures can predict the likelihood of PNF, good function, or EGD in DCD liver transplants.
Main Methods:
- MicroRNA was extracted from archival formalin-fixed, post-perfusion tru-cut liver biopsies from DCD donors.
- High-throughput miRNA expression analysis was conducted using miRNA arrays.
- Bioinformatics analysis and real-time quantitative PCR (RT-qPCR) were used for data validation and miRNA function prediction.
Main Results:
- Array analysis identified 16 differentially expressed miRNAs (p<0.05) between DCD liver groups.
- RT-qPCR confirmed high expression of miR-155 and miR-940 across all clinical outcome groups.
- Only miR-22 showed marginal differential expression significance (p=0.049) between the three DCD clinical outcome groups.
Conclusions:
- MicroRNA expression patterns demonstrated a low diagnostic potential for clinically discriminating DCD liver quality and predicting transplant outcomes.
- miR-22 was computationally predicted to influence signaling pathways involved in protein turnover, metabolism, and apoptosis/cell cycle.
- Further investigation into other molecular markers may be necessary to enhance the prediction of DCD liver graft viability.
