Advancements in Predictive Tools for Primary Graft Dysfunction in Liver Transplantation: A Comprehensive Review

Highlights What are the main findings? Primary graft dysfunction (PGD) involves early allograft dysfunction (EAD) and more severe primary nonfunction (PNF), both stemming from ischemia-reperfusion injury (IRI). Accurate and early diagnosis of PGD is crucial to the retransplantation decision-making process and the implementation of future mitigation strategies. Novel tools for predicting PNF utilize serum markers, marker-derived models, tissue biopsy analysis, metabolomics, evaluations of organ perfusion and liver metabolism, and assessments of graft perfusate during machine perfusion. What is the implication of the main finding? The current implementation of extended criteria donors (ECD) exacerbates the limitations of the binary EAD criteria and has prompted a refreshed approach to the graft dysfunction assessment protocol. Recently, new serum parameters have been associated with EAD occurrence, and their incorporation into graft dysfunction evaluations may improve accuracy.Highlights What are the main findings? Primary graft dysfunction (PGD) involves early allograft dysfunction (EAD) and more severe primary nonfunction (PNF), both stemming from ischemia-reperfusion injury (IRI). Accurate and early diagnosis of PGD is crucial to the retransplantation decision-making process and the implementation of future mitigation strategies. Novel tools for predicting PNF utilize serum markers, marker-derived models, tissue biopsy analysis, metabolomics, evaluations of organ perfusion and liver metabolism, and assessments of graft perfusate during machine perfusion. What is the implication of the main finding? The current implementation of extended criteria donors (ECD) exacerbates the limitations of the binary EAD criteria and has prompted a refreshed approach to the graft dysfunction assessment protocol. Recently, new serum parameters have been associated with EAD occurrence, and their incorporation into graft dysfunction evaluations may improve accuracy.Abstract Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.