Hypothermic Machine Perfusion for Liver Graft Preservation

This is a prospective, single-center, randomized controlled clinical trial designed to evaluate the impact of hypothermic machine perfusion on liver graft preservation and post-transplant outcomes in adult liver transplantation.

Liver transplantation is the standard treatment for end-stage liver disease; however, outcomes are strongly influenced by graft quality. The increasing use of extended criteria donors has introduced additional challenges, as these grafts are more susceptible to ischemia-reperfusion injury, a key determinant of early graft dysfunction and post-transplant complications. Conventional static cold storage, although widely used, does not prevent ongoing anaerobic metabolism and progressive depletion of cellular energy stores, contributing to mitochondrial dysfunction, oxidative stress, and inflammatory activation upon reperfusion.

Hypothermic machine perfusion has emerged as an alternative preservation strategy by providing continuous oxygenated perfusion under controlled hypothermic conditions. This approach aims to preserve mitochondrial integrity, reduce metabolic stress, and mitigate ischemia-reperfusion injury, thereby potentially improving graft viability and expanding the utilization of marginal organs.

In this study, liver grafts from deceased donors will be allocated to either hypothermic machine perfusion or conventional static cold storage. Following procurement, grafts assigned to the intervention group will undergo ex situ hypothermic perfusion using an oxygenated preservation solution under controlled conditions, while the control group will follow standard institutional preservation protocols.

All transplant procedures and perioperative management will be conducted according to institutional standards. Post-transplant follow-up will include clinical and laboratory monitoring to assess graft function and detect complications.

Donor-related inclusion criteria:

• Liver donors with confirmed diagnosis of brain death.
• Extended criteria donors (ECD).
• Age ≥18 years.
• Family consent for organ donation obtained.
• Negative serology for HTLV, HIV, Chagas disease, and hepatitis B and C.

Recipient-related inclusion criteria:

• Adult patients (≥18 years) undergoing liver transplantation.
• Diagnosis of end-stage liver disease or indication for liver transplantation.
• Candidates for primary liver transplantation.
• Ability to understand and provide written informed consen

Donor-related exclusion criteria:

• Presence of moderate or severe hepatic steatosis.
• Pediatric donors.
• Donors classified as ideal, defined by the simultaneous presence of all of the following criteria: Age <35 years, Body mass index (BMI) <28 kg/m², No history of cardiopulmonary resuscitation, Norepinephrine requirement <0.5 µg/kg/min, Liver enzymes (AST or ALT) ≥2 times the upper limit of normal, Intensive care unit stay ≤7 days

Recipient-related exclusion criteria:

• Complex portal vein thrombosis (grade III or IV).
• Combined or dual organ transplantation.
• Retransplantation.
• Acute liver failure.
• MELD score >30.
• History of multiple prior liver or biliary surgeries.