Machine perfusion techniques for liver transplantation - A meta-analysis of the first seven randomized-controlled trials

Alessandro Parente; Fabio Tirotta; Alessia Pini; Janina Eden; Daniele Dondossola; Tommaso M Manzia; Philipp Dutkowski; Andrea Schlegel

doi:10.1016/j.jhep.2023.05.027

Machine perfusion techniques for liver transplantation - A meta-analysis of the first seven randomized-controlled trials

J Hepatol. 2023 Nov;79(5):1201-1213. doi: 10.1016/j.jhep.2023.05.027. Epub 2023 Jun 9.

Authors

Alessandro Parente¹, Fabio Tirotta², Alessia Pini³, Janina Eden⁴, Daniele Dondossola⁵, Tommaso M Manzia¹, Philipp Dutkowski⁴, Andrea Schlegel⁶

Affiliations

¹ HPB and Transplant Unit, Department of Surgical Science, University of Rome Tor Vergata, Rome, Italy.
² Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom.
³ Department of Statistical Sciences, Università Cattolica del Sacro Cuore, Milan, Italy.
⁴ Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland.
⁵ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, General and Liver Transplant Surgery Unit, Milan, 20122, Italy; Department of Pathophysiology and Transplantation Università degli Studi di Milano, Italy.
⁶ Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, General and Liver Transplant Surgery Unit, Milan, 20122, Italy; Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: Schlegel.andrea@outlook.de.

PMID: 37302578
DOI: 10.1016/j.jhep.2023.05.027

Abstract

Background & aims: Machine perfusion is increasingly being tested in clinical transplantation. Despite this, the number of large prospective clinical trials remains limited. The aim of this study was to compare the impact of machine perfusion vs. static cold storage (SCS) on outcomes after liver transplantation.

Methods: A systematic search of MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify randomized-controlled trials (RCTs) comparing "post-transplant" outcomes following machine perfusion vs. SCS. Data were pooled using random effect models. Risk ratios (RRs) were calculated for relevant outcomes. The quality of evidence was rated using the GRADE-framework.

Results: Seven RCTs were identified (four on hypothermic oxygenated [HOPE] and three on normothermic machine perfusion [NMP]), including a total number of 1,017 patients. Both techniques were associated with significantly lower rates of early allograft dysfunction (NMP: n = 41/282, SCS: n = 74/253, RR 0.50, 95% CI 0.30-0.86, p = 0.01, I² = 39%; HOPE: n = 45/241, SCS: n = 97/241, RR 0.48, 95% CI 0.35-0.65, p < 0.00001, I² = 5%). The HOPE approach led to a significant reduction in major complications (Clavien Grade ≥IIIb; HOPE: n = 90/241; SCS: n = 117/241, RR 0.76, 95% CI 0.63-0.93, p = 0.006, I² = 0%), "re-transplantation" (HOPE: n = 1/163; SCS: n = 11/163; RR 0.21, 95% CI 0.04-0.96, p = 0.04; I² = 0%) and graft loss (HOPE: n = 7/163; SCS: n = 19/163; RR 0.40, 95% CI 0.17-0.95, p = 0.04; I² = 0%). Both perfusion techniques were found to 'likely' reduce overall biliary complications and non-anastomotic strictures.

Conclusions: Although this study provides the highest current evidence on the role of machine perfusion, outcomes remain limited to a 1-year follow-up after liver transplantation. Comparative RCTs and large real-world cohort studies with longer follow-up are required to enhance the robustness of the data further, thereby supporting the introduction of perfusion technologies into routine clinical practice.

Prospero-registration: CRD42022355252.

Impact and implications: For a decade, two dynamic perfusion concepts have increasingly been tested in several transplant centres worldwide. We undertook the first systematic review and meta-analysis and identified seven published RCTs, including 1,017 patients, evaluating the effect of machine perfusion (hypothermic and normothermic perfusion techniques) compared to static cold storage in liver transplantation. Both perfusion techniques were associated with lower rates of early allograft dysfunction in the first week after liver transplantation. Hypothermic oxygenated perfusion led to a reduction in major complications, lower "re-transplantation" rates and better graft survival. Both perfusion strategies were found to 'likely' reduce overall biliary complications and non-anastomotic biliary strictures. This study provides the highest current evidence on the role of machine perfusion. Outcomes remain limited to a 1-year post-transplant follow-up. Larger cohort studies with longer follow-up and clinical trials comparing the perfusion techniques are required. This is especially relevant to provide clarity and optimise implementation processes further to support the commissioning of this technology worldwide.

Keywords: hypothermic oxygenated perfusion; liver transplantation; machine perfusion; normothermic machine perfusion; randomized-controlled trial; static cold storage.