Advanced Machine-Assisted Liver Reconditioning in Critical Care

Abstract

Liver transplantation (LT) remains the definitive treatment for end-stage liver disease, but it continues to face two major challenges: ischemia-reperfusion injury (IRI), which compromises graft function, and a critical shortage of suitable donor organs. To address the latter, the use of marginal grafts from extended criteria donors (ECD) and donation after circulatory death (DCD) has increased, although these organs are more susceptible to IRI. This review aims to evaluate the current landscape of machine perfusion (MP) technologies—hypothermic, subnormothermic, and normothermic—and their role in improving graft preservation, function, and utilization in LT. MP has emerged as a promising alternative to static cold storage (SCS), offering the potential to assess graft viability and reduce IRI. Hypothermic machine perfusion (HMP), particularly when oxygenated (HOPE), shows protective effects on the biliary system and may reduce ischemic injury, though data on improved graft survival remain limited. Subnormothermic perfusion is associated with enhanced ATP restoration and reduced cold-induced injury in preclinical models but lacks robust clinical validation. Normothermic machine perfusion (NMP) allows real-time functional assessment and supports active metabolism, with clinical trials demonstrating reduced early allograft dysfunction and increased use of marginal grafts. Recent studies suggest that combining techniques, such as HOPE followed by NMP, may offer synergistic benefits, although optimal protocols remain under investigation. Machine perfusion technologies represent a significant advancement in liver transplantation by improving preservation strategies and enabling the use of suboptimal grafts. While NMP appears most promising for functional assessment and extended preservation, HOPE shows particular value in end-ischemic reconditioning. Although MP is not yet a complete replacement for SCS, its potential to improve outcomes and expand the donor pool is increasingly supported by emerging clinical evidence. Further large-scale, randomized trials are essential to determine best practices and establish MP as a standard component of LT protocols.