Early allograft dysfunction discovery and prognosis: does the Model for End-stage Liver Disease still prevail?

We read with great interest in the article by Luo et al. about comparison among Olthoff criteria, the Model for End-stage Liver Disease (MELD) score on postoperative day 5 (MELDPOD5), and the Model for Early Allograft Function scoring (MEAF) on their prognostic value for post-transplant graft and patient survival (1). Though all three metrics discriminated the high-risk patients from others effectively, MELDPOD5 displayed quite an advantage over MEAF and Olthoff criteria in predicting 3-month graft survival. Moreover, donor body mass index, donor risk index, intraoperative transfusions, recipient hypertension, and preoperative total bilirubin were identified as predictive factors for MELDPOD5-defined early allograft dysfunction (EAD).

Since EAD is a clinical diagnosis rather than a histopathological term, gold standards including biopsy are not applicable in this situation, and different diagnostic criteria or scoring systems should be naturally calibrated to patients’ prognosis. As the first definite system and the most widely accepted one, Olthoff criteria was born from the summation of clinical practice and was then assessed for predicting allograft loss or death (2). MEAF was designed to be a numerical scale for EAD diagnosis: alanine aminotransferase, international normalized ratio, and bilirubin were linearized and then attributed with the same weights in the final formula—the maximum possible values of the three terms were all 3.33 (3). Both Olthoff criteria and MEAF subjectively treat different laboratory findings relatively equally, which might compromise their diagnostic and prognostic performances.

The MELD, on the other hand, was developed initially with Cox proportional-hazards regression for short-term survival of cirrhotic patients after transjugular intrahepatic portosystemic shunt (4). In this way, the hazard ratio from regression served as proper weights for different laboratory findings with an objective, statistical basis. It was quickly extrapolated to various other chronic liver disease settings, and finally accepted as a tool for liver allocation after several amendments regarding the sickest-first priority (5). Though several attempts have been made to explore the long-term prognostic value of pre-transplant MELD before (6), it was not until 2013 that MELD was formally extrapolated to post-transplant population with satisfactory performances (7). Nevertheless, it remains controversial whether the pre-transplant recipient sieving with MELD adds to its post-transplant prognostic strength, and whether the weights of different laboratory findings should be adjusted since post-transplant patients are relieved of “end-stage liver diseases”. Moreover, integrating all laboratory tests into one score might lose information, since a recent study reported that EAD patients with merely either aminotransferase elevated had comparable graft and patient survival to those of patients without EAD (8).

Recipient preoperative systemic hypertension was identified as a risk factor for EAD in this article for the first time. The aberrant levels of vasoactive agents and compromised arteriole constriction-relaxation might contribute to the hazard imposed by systemic hypertension, and further studies should be conducted to confirm this effect. It has been recognized that the donor condition exerted a significant impact on the risk of EAD. Considering the paucity of donated liver, marginal donor has been increasingly adopted to extend life expectancy of those with longer waiting time (9). Since the cohort featured a relatively high proportion of tumor as the indication, we suggest the authors to perform subgroup analysis in order to clarify the effect of donor condition on EAD in tumor patients. This information could be of great help for tumor patients to weigh benefits versus risks of accepting a compromised allograft. With the emerging machine perfusion technology, ex vivo repairing of allografts before implantation might serve as an alternative in the near future (10). Clinical trials, including Bridge for HOPE: Hypothermic Oxygenated Perfusion Versus Cold Storage Prior to Liver Transplantation (ClinicalTrials.gov identifier NCT05045794), are under way, and we are looking forward to the new hope for patients and their family.

Acknowledgments

Funding: This work was supported by Capital’s Funds for Health Improvement and Research (No. 2020-1-2024).

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-22-758/coif). The authors have no conflicts of interest to declare.

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