Early Allograft Dysfunction

The ARANMP-LT study is a multicenter, open-label, randomized, parallel-group, non-inferiority clinical trial designed to evaluate whether avoiding graft recooling after normothermic machine perfusion (NMP) improves early outcomes following liver transplantation. Although graft recooling before implantation is common practice, experimental and preliminary clinical evidence suggests that abrupt temperature changes may contribute to ischemia-reperfusion injury. Adult recipients of deceased-donor liver grafts preserved with NMP or sequential hypothermic-normothermic machine perfusion (SHNMP) will be randomized in a 1:1 ratio to either standard graft implantation with recooling using cold preservation solution (control group) or implantation without recooling using a room-temperature 5% albumin flush immediately before reperfusion (intervention group). The primary objective is to compare the incidence of Early Allograft Dysfunction (EAD), defined according to the Olthoff criteria, between the two treatment groups. Secondary objectives include evaluation of histopathological ischemia-reperfusion injury using the Suzuki score, vascular and biliary complications, primary non-function, post-reperfusion syndrome, patient and graft survival, length of intensive care unit and hospital stay, perioperative transfusion requirements, and safety outcomes. A total of 170 participants will be enrolled across multiple Italian liver transplant centers and followed for 90 days after transplantation.

Early allograft dysfunction (EAD) remains one of the most important complications following orthotopic liver transplantation (OLT). Currently, there is no established intraoperative biomarker that reliably predicts graft dysfunction at an early stage. Near-infrared spectroscopy (NIRS) combined with the vascular occlusion test (VOT) is a non-invasive method for assessing tissue oxygenation and microcirculatory reserve. This prospective observational study aims to investigate whether VOT-derived parameters, including desaturation slope, recovery slope and post-ischemic hyperemic area under the curve (AUC-H), can predict EAD in liver transplant recipients. Measurements will be performed at four predefined intraoperative timepoints: after induction of anesthesia, during the anhepatic phase, during the neohepatic phase and at the end of surgery. The primary outcome is the occurrence of EAD according to Olthoff criteria.

Liver transplantation is a life-saving treatment for patients with severe liver disease. Because of the shortage of donor organs, transplant centers increasingly use donor livers that may be more vulnerable to injury and dysfunction. To improve the quality of these organs before transplantation, many centers use hypothermic oxygenated machine perfusion (HOPE or D-HOPE), a technique that preserves the liver under cold, oxygenated conditions. However, there are currently no widely accepted methods to determine whether a liver is functioning well enough during this preservation process. The purpose of this study is to investigate whether changes observed in liver tissue during hypothermic machine perfusion can help predict how well the transplanted liver will function after surgery. The study will compare liver biopsy samples collected before and after one hour of perfusion and will analyze biological markers released into the perfusion fluid, including markers of mitochondrial injury and inflammation. The main question this study aims to answer is whether histological changes occurring during hypothermic perfusion, alone or in combination with biochemical biomarkers, can accurately predict liver graft viability and post-transplant outcomes. Researchers will also evaluate whether these data can be used to develop an artificial intelligence-based model to support clinical decision-making during organ preservation. A total of 150 adult liver transplant recipients receiving donor livers treated with HOPE or D-HOPE will be enrolled at three Italian liver transplant centers. Participants will be followed for 90 days after transplantation to assess liver graft function, graft survival, patient survival, and post-transplant complications. The results of this study may improve the assessment of donor liver quality before transplantation and help clinicians make more informed decisions about organ use, ultimately increasing the safety and effectiveness of liver transplantation.