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Organ preservation; Normothermic machine perfusion; Liver transplantation; Extended criteria donors; Graft viability assessment; Hepatic ischemia-reperfusion injury; Ex vivo liver perfusion; Transplant outcomes; Dynamic preservation; Organ reconditioning

Introduction

Liver transplantation remains the definitive treatment for end-stage liver disease, but the growing disparity between the number of patients on transplant waitlists and the availability of suitable donor organs has created an urgent need to optimize organ utilization [1-5]. Traditional static cold storage (SCS), the standard method for organ preservation, has shown limitations in preventing ischemia-reperfusion injury and preserving marginal or extended criteria donor (ECD) grafts. In response, normothermic machine perfusion (NMP) has emerged as a promising preservation technology that maintains the liver at physiological temperature (37°C) during ex vivo perfusion, enabling real-time viability assessment, cellular repair, and extended preservation windows. This review explores the technological advancements, clinical applications, and outcomes associated with NMP in liver transplantation [6-10].

Discussion

Normothermic machine perfusion utilizes oxygenated perfusate enriched with nutrients, red blood cells, and medications to mimic in vivo conditions, thereby maintaining hepatic metabolism and reducing cold ischemic injury. Compared to SCS, NMP preserves mitochondrial function, limits oxidative stress, and reduces hepatocellular damage. Recent trials have demonstrated that livers preserved with NMP exhibit lower peak AST/ALT levels post-transplantation, shorter intensive care unit stays, and better early graft function.

A significant advantage of NMP lies in its ability to support the use of ECD livers—organ from donors with steatosis, older age, cardiac death, or prolonged warm ischemia. With SCS, many such livers are discarded due to high risk of dysfunction. However, NMP allows transplant teams to evaluate dynamic biomarkers such as lactate clearance, bile production, perfusate transaminases, and hemodynamic stability, enabling informed go/no-go decisions. As a result, centers employing NMP have reported a reduction in discarded livers and a corresponding increase in transplantation rates.

Further, NMP has opened avenues for organ repair and reconditioning. Studies suggest that during perfusion, pharmacological agents, anti-inflammatory cytokines, and gene therapies could be introduced to improve organ quality prior to implantation. In some cases, steatotic livers have been partially defatted, improving transplant eligibility. Additionally, innovations in perfusion device design, including portable systems and automated control modules, have enhanced ease of use and safety.

Despite these benefits, NMP is not without challenges. Cost and resource requirements are higher than SCS, with machines and perfusate solutions requiring careful regulation. Protocol standardization across transplant centers is still evolving, and long-term outcomes beyond the first year post-transplant require further study. Nevertheless, landmark trials such as the VITTAL study and PROTECT trial have validated the safety and efficacy of NMP, and its adoption is expanding globally.

Conclusion

Normothermic machine perfusion represents a transformative advance in liver transplantation, offering superior graft preservation, viability assessment, and expanded utilization of marginal donor livers. By maintaining physiological conditions ex vivo, NMP reduces ischemia-reperfusion injury, enables organ reconditioning, and improves short-term transplant outcomes. Although logistical and financial challenges remain, ongoing clinical trials and increasing institutional experience are paving the way for widespread implementation. As protocols mature and costs decrease, NMP has the potential to become the new standard of care in liver transplantation, significantly addressing the organ shortage crisis while enhancing patient outcomes.

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