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

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.

Keywords: graft preservation; liver transplantation; machine perfusion; meta-analysis; static cold storage.

Figure 1

Flowchart showing search strategy with inclusions and exclusions.

Figure 2

Meta-analysis on posttransplant peak AST/ALT levels between MP and CS preservation. (A) AST level. MP reduced posttransplant peak AST level (SMD = −0.53; 95% CI = −1.04 to −0.02; P = 0.04), (B) ALT level. MP tends to reduce posttransplant peak AST level (SMD = −0.44; 95% CI = −0.91 to −0.02; P = 0.06). MP, machine perfusion; CS, cold storage; SMD, standardized mean difference; CI, confidence interval.

Figure 3

Meta-analysis on EAD rates between MP and CS preservation. HMP reduced the EAD rates (OR = 0.49; 95% CI = 0.27–0.88; P = 0.02), and NMP reduced the EAD rates (OR = 0.34; 95% CI = 0.20–0.59; P = 0.0001). EAD, early allograft dysfunction; MP, machine perfusion; CS, cold storage; HMP, hypothermic machine perfusion; NMP, normothermic machine perfusion; CI, confidence interval.

Figure 4

Meta-analysis on PNF rates between MP and CS preservation. MP cannot reduce the PNF rates (OR = 0.60; 95% CI = 0.14–2.60; P = 0.49). Data are expressed as OR ± 95% CI. PNF, primary nonfunction; MP, machine perfusion; CS, cold storage; CI, confidence interval.

Figure 5

Meta-analysis on total biliary complications rates between MP and CS preservation. HMP reduced the total biliary complications (OR = 0.45; 95% CI = 0.25–0.80; P = 0.007), but NMP cannot reduce the total biliary complications (OR = 0.70; 95% CI = 0.34–1.46; P = 0.34). MP, machine perfusion; CS, cold storage; HMP, hypothermic machine perfusion; NMP, normothermic machine perfusion; CI, confidence interval.

Figure 6

Meta-analysis on ischemic cholangiopathy rates between MP and CS preservation. HMP reduced the ischemic cholangiopathy rates (OR = 0.25; 95% CI = 0.08–0.73; P = 0.01), and NMP cannot reduce the ischemic cholangiopathy rates (OR = 0.76; 95% CI = 0.24–2.38; P = 0.64). Data are expressed as OR ± 95% CI. MP, machine perfusion; CS, cold storage; HMP, hypothermic machine perfusion; NMP, normothermic machine perfusion; CI, confidence interval.