HOPE Reduces Early Liver Graft Dysfunction : JAMA Surg | May 2026

Introduction:

Introduction: Liver transplantation increasingly relies on extended-criteria donor (ECD) and donation-after-circulatory-death (DCD) grafts to address organ shortages. However, these grafts are more susceptible to ischemia-reperfusion injury, which contributes to early allograft dysfunction (EAD), prolonged hospitalization, biliary complications, and inferior post-transplant outcomes. Hypothermic oxygenated perfusion (HOPE) has emerged as a promising preservation strategy that restores mitochondrial function and reduces reperfusion injury before implantation.

Problem Statement:

Problem Statement: Although European studies have demonstrated benefits of HOPE, evidence supporting its effectiveness in a multicenter US transplant population using higher-risk donor livers has remained limited. Whether portal-venous HOPE can meaningfully improve graft function and clinical outcomes compared with conventional static cold storage (SCS) required prospective randomized evaluation.

Summary:

Summary: The Bridge to HOPE Trial was a multicenter randomized clinical trial conducted across 15 US liver transplant centers, enrolling 219 recipients of extended-criteria donor livers, including both donation-after-brain-death (DBD) and DCD grafts. Patients were randomized to receive either conventional static cold storage alone or portal-venous hypothermic oxygenated perfusion following transport and before implantation.

The primary endpoint was early allograft dysfunction. HOPE significantly reduced EAD compared with static cold storage alone, occurring in 20.2% of recipients versus 37.3% in the control group. This represents a clinically meaningful reduction in early graft injury and demonstrates the capacity of oxygenated machine perfusion to improve immediate graft performance.

Recipients receiving HOPE also achieved significantly better Model for Early Allograft Function (MEAF) scores, indicating superior early hepatic recovery after transplantation. Furthermore, HOPE was associated with a shorter hospital stay, suggesting faster postoperative recovery and reduced healthcare utilization.

Importantly, the intervention was safe and easily integrated into routine transplant workflows. One-year patient survival and graft survival were excellent in both groups and did not significantly differ, reflecting the overall high success rates of contemporary liver transplantation.

Although rates of non-anastomotic biliary strictures were not significantly different, post hoc analyses suggested fewer cases of graft loss related to biliary complications in the HOPE group. Major postoperative complications were also numerically lower among HOPE recipients.

The biological rationale for HOPE lies in its ability to oxygenate the graft under hypothermic conditions before reperfusion. This process replenishes mitochondrial energy stores, reduces oxidative stress, limits inflammatory activation, and minimizes ischemia-reperfusion injury. These mechanisms are particularly important for marginal donor grafts, where preservation injury contributes substantially to early dysfunction.

The study is notable because it evaluated a pragmatic “back-to-base” preservation strategy that can be implemented without requiring continuous machine perfusion during transport. This makes adoption more feasible for transplant programs compared with more complex normothermic perfusion systems.

Overall, this landmark randomized trial demonstrates that portal-venous HOPE significantly reduces early allograft dysfunction, improves early graft function, and shortens hospital stay in recipients of extended-risk liver grafts. These findings support HOPE as an effective and practical preservation strategy that may improve outcomes as transplant programs increasingly utilize higher-risk donor organs.