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Waste Not, Want Not: Determining the Fate of the Marginal Liver Allograft

Dr. John SealJohn Seal, MD
Transplant Surgeon
Ochsner Health System

The primary goal of liver transplantation is to reduce mortality and significant morbidity associated with end stage liver disease and hepatocellular carcinoma. To that end, the current allocation system in the United States is designed to prioritize patients with the highest risk of death as estimated by the MELD scoring system. However, significant variability in the quality of donor organs complicates this process. The presence of extended criteria donor (ECD) features such as advanced age, abnormal liver function tests, steatosis, and donation-after-circulatory death can negatively impact early allograft function and overall graft survival. Many transplant surgeons avoid or very selectively use these grafts in the highest MELD patients out of concern for early organ dysfunction not well tolerated by sicker patients. In the environment of severe organ shortage, transplant centers are left with the onerous task of balancing the risk of death on the waitlist versus the potential risks associated with expanded criteria allografts.  Each organ offer prompts the questions: Will this liver work in my sickest patient? If not, will it work in any of my listed patients? And, if it will only work in my lowest MELD patients, am I really offering a survival benefit?

For the past several years, our center has adopted an aggressive approach to organ utilization based on the hypothesis that the potentially deleterious effects of marginal features can be minimized through careful patient selection and minimization of cold ischemia time. Recipient selection is focused on limiting surgical complexity to facilitate a rapid hepatectomy with minimal blood loss. We carefully consider the patient’s overall functional status and co-morbidities to help predict an adequate physiologic reserve to support hemodynamic stability during clamp and reperfusion periods. During the transplant evaluation process, patients are assigned a score of surgical risk to facilitate recipient selection when an ECD offer is received. The second key principle, minimization of cold ischemia time, is more complex—it requires robust logistics and communications with procurement coordinators as well as an OR staff and anesthesia team able to mobilize quickly and on short notice. We also have a routine practice of having two attending surgeons available for every case. By executing these details well, we can avoid the cumulative effects of even small delays in the process that can add hours to cold ischemia time.

While the upper limit of recipient selection for ECD is easier to define (high MELD, ICU, frail, etc.), the lower limit is less clear. In keeping with the priorities of the allocation system, we approach each offer systematically working our way down the list of potential recipients from high MELD score to low. Our goal is to transplant the graft into the most appropriate patient with the highest MELD on the list. A majority of the recipients of imported grafts at our center have MELD scores between 18-25, a range where the survival benefit from transplantation is clear. For the lowest MELD patients (<18), we focus on patients with a disease burden that is not reflected in their MELD score such as marked ascites, debilitating encephalopathy, or early stage HCC tumors waiting to accrue exception points. Also, it is important to consider the MELD history of the patient, including prior episodes of increased MELD suggesting instability in the degree of compensation and likelihood of progressive liver disease in the future.

What does it mean for a graft to “work”? Defining the terms of early allograft dysfunction is critical to evaluating the performance of ECD grafts. Since 2012, we have observed no significant difference in graft or patient survival comparing imported ECD grafts with standard donors, with both categories at or above expected. Certainly we have seen higher rates of elevated AST/ALT (>2000) in the ECD grafts, but typically it is transient and normalizes by the time of discharge from the hospital. At our center we put more weight on the markers of synthetic and metabolic function of the graft, namely INR, bilirubin, and lactate in the early post-transplant period. Using post-transplant MELD as a marker of graft function1, we see no difference in early graft function with ECD grafts.

We believe nearly every donor liver offers a potential survival benefit for some listed patient. Accordingly, we have invested resources and experience to optimize outcomes using ECD grafts and to identify suitable recipients to achieve a survival benefit.  Currently in the United States, the distribution of aggressive centers and donor liver utilization varies significantly between regions.2,3 As we strive for parity in organ allocation across regions, some emphasis should be placed on the lack of uniformity in utilization. We should also continue to invest in the development of better diagnostics for graft assessment, including normothermic machine perfusion systems4 and metabolomic/proteomic approaches to biomarker discovery5. But in the meantime, the challenge is to employ donor-recipient matching strategies to optimize utilization of the non-perfect graft within an allocation system that prioritizes our sickest patients.

References

1. Wagener G, Raffel B, Young AT, Minhaz M, Emond J. Predicting early allograft failure and mortality after liver transplantation: the role of the postoperative model for end-stage liver disease score. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2013 May;19(5):534–42.

2. Garonzik-Wang JM, James NT, Van Arendonk KJ, Gupta N, Orandi BJ, Hall EC, et al. The aggressive phenotype revisited: utilization of higher-risk liver allografts. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2013 Apr;13(4):936–42.

3. Goldberg DS, French B, Lewis JD, Scott FI, Mamtani R, Gilroy R, et al. Liver transplant center variability in accepting organ offers and its impact on patient survival. J Hepatol. 2015 Nov 25;

4. Ravikumar R, Jassem W, Mergental H, Heaton N, Mirza D, Perera MTPR, et al. Liver transplantation after ex vivo normothermic machine preservation: a Phase 1 (first-in-man) clinical trial. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2016 Jan 11;

5. Cortes M, Pareja E, García-Cañaveras JC, Donato MT, Montero S, Mir J, et al. Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction. J Hepatol. 2014 Sep;61(3):564–74.

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