Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD)

Abstract

IntroductionOrthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT.Methods and analysisHOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1–2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia–reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT.Ethics and disseminationThe study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018.Trial registration numberNCT03124641.

Machine perfusion for liver transplantation in the era of marginal organs—New kids on the block

“…In this context, the implementation and clinical effects of HOPE have not yet been thoroughly investigated. The first multicentre RCT focusing on ECD‐DBD liver transplantation, initiated by our group, started recruiting in September 2017 at the RWTH University Hospital Aachen in Germany . The primary endpoint of the HOPE‐ECD‐DBD trial is early graft injury, assessed by peak ALT during the first 7 days post‐transplantation.…”

“…Current clinical strategies are unable to fulfil the demands presented by the transplantation of so‐called marginal grafts, and the need for optimized preservation techniques that address the underlying impairment of ECD allografts is paramount. In recent years, the main research focus of several groups, including ours, has therefore been the development of improved organ preservation and organ conditioning approaches . Machine perfusion (MP) has been recognized as a promising preservation strategy in the context of OLT using ECD allografts.…”

“…In recent years, the main research focus of several groups, including ours, has therefore been the development of improved organ preservation and organ conditioning approaches. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Machine perfusion (MP) has been recognized as a promising preservation strategy in the context of OLT using ECD allografts. While SCS only prolongs storage time and limits the damage sustained during the period of cold ischaemia, MP even appears to be capable of reversing some of these effects.…”

Implementing an innovated preservation technology: The American Society of Transplant Surgeons’ (ASTS) Standards Committee White Paper on Ex Situ Liver Machine Perfusion

“…37 Organs randomized to the HOPE ECD-DBD protocol will receive 1-2 hours of hypothermic portal perfusion and will be compared with SCS in HTK solution. 37 Organs randomized to the HOPE ECD-DBD protocol will receive 1-2 hours of hypothermic portal perfusion and will be compared with SCS in HTK solution.…”

“…Similar in design to the HOPE trials, the HOPE ECD-DBD will randomize patients receiving ECD livers, which were defined as age > 65, ICU treatment > 7 days, donor body mass index (BMI) > 30, > 40% macrosteatosis, serum sodium > 165 mmol/L, AST or ALT > 3 times normal, or a serum bilirubin > 2 mg/dL. 37 Organs randomized to the HOPE ECD-DBD protocol will receive 1-2 hours of hypothermic portal perfusion and will be compared with SCS in HTK solution. The primary endpoint of the trial is peak transaminase levels.…”