A Systematic Review and Meta-Analysis of Machine Perfusion vs. Static Cold Storage of Liver Allografts on Liver Transplantation Outcomes: The Future Direction of Graft Preservation.

Yu Nie,Lin Zhou,Jianhui Li,Jun Yu,Haiyang Xie,Junjun Jia,Shu-Sen Zheng

doi:10.3389/fmed.2020.00135

Abstract

Background: Machine perfusion (MP) and static cold storage (CS) are two prevalent methods for liver allograft preservation. However, the preferred method remains controversial.Aim: To conduct a meta-analysis on the impact of MP preservation on liver transplant outcome.Methods: PubMed, EMBASE, and Cochrane Library databases were systematically searched to identify relevant trials comparing the efficacy of MP vs. CS. Odds ratios (OR) and fixed-effects models were calculated to compare the pooled data.Results: Ten prospective cohort studies and two randomized controlled trials (RCTs) were included (MP livers vs. CS livers = 315:489). Machine perfusion demonstrated superior outcomes in posttransplantation aspartate aminotransferase levels compared to CS (P < 0.05). The overall incidence of early allograft dysfunction (EAD) was significantly reduced with MP preservation than CS [OR = 0.46; 95% confidence interval (CI) = 0.31–0.67; P < 0.0001]. The incidence of total biliary complications (OR = 0.53; 95% CI = 0.34–0.83; P = 0.006) and that of ischemic cholangiopathy (OR = 0.39; 95% CI = 0.18–0.85; P = 0.02) were significantly lower in recipients with MP preservation compared with CS preservation. Hypothermic machine perfusion (HMP) but not normothermic machine perfusion (NMP) was found to significantly protect grafts from total biliary complications and ischemic cholangiopathy (P < 0.05). However, no significant differences could be detected utilizing either HMP or NMP in primary nonfunction, hepatic artery thrombosis, postreperfusion syndrome, 1-year patient survival, or 1-year graft survival (P > 0.05).Conclusions: Machine perfusion is superior to CS on improving short-term outcomes for human liver transplantation, with a less clear effect in the longer term. Hypothermic machine perfusion but not NMP conducted significantly protective effects on EAD and biliary complications. Further RCTs are warranted to confirm MP's superiority and applications.

Highlights

Liver transplantation (LT) has been the optimal treatment for patients with end-stage liver disease
After excluding ineligible publications based on the selection and exclusion criteria, 12 studies, including 10 nonrandomized prospective phase I clinical trials (10, 21–29), one multiinstitutional randomized study (18), and one single-center, randomized controlled study (30), were eventually included in the meta-analysis of the comparison between machine perfusion (MP) and cold storage (CS) on clinical outcomes in LT
In the 12 included studies, five studies used hypothermic machine perfusion (HMP), whereas the other seven studies investigated normothermic machine perfusion (NMP). Of these 12 studies, seven were from European institutes, including four single-center prospective trials, one multicenter prospective trials (22, 25–27), one prospective multicenter randomized controlled trial (RCT) (18), and one single-center, randomized controlled study (30); two single-center prospective trials were from Canadian institutes (23, 24), whereas the remaining three studies were from the US institutes (10, 21)

Summary

Introduction

Liver transplantation (LT) has been the optimal treatment for patients with end-stage liver disease. Increasing demands for LT have caused severe shortage of donor liver organs in clinical application. To overcome this discrepancy, donation after circulatory death (DCD), extended criteria donors (ECDs), living liver donation, or marginal liver grafts are increasingly accepted to expand the limited donor pool. Standard static cold storage (CS) remains the gold standard method for liver graft preservation. The effectiveness of CS preservation is currently unable to provide sufficient protection of liver grafts against IRI, especially for prolonged CS of DCD and marginal livers, often resulting in increased risk of EAD, PNF, and biliary complications (2). Machine perfusion (MP) and static cold storage (CS) are two prevalent methods for liver allograft preservation.

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