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). Jia et al. Machine Perfusion: Future Preservation Method 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.

Methaemoglobinaemia Can Complicate Normothermic Machine Perfusion of Human Livers

“…However, due to a multitude of transplant logistics, prolonged preservation is often needed. Perhaps a hypothermic oxygenated perfusion approach, where an oxygen carrier is not required, could be better suited for storage and reconditioning of steatotic grafts akin to those described above ( 11 ).…”

Necroptosis in Hepatosteatotic Ischaemia-Reperfusion Injury

“…During transplantation, donor liver preservation is a critical step to maintaining the quality of liver as well as to improve post-transplant outcomes. Conventional static cold storage (SCS) is considered to be the primary method for organ preservation [ 219 , 220 ]. However, if it is prolonged, this method does not provide sufficient protection against IR injury particularly for the marginal livers such as steatotic livers and DCD livers which are already in a vulnerable state.…”

The Role of Metabolomics in Current Concepts of Organ Preservation

“…Rapidly increasing demands for liver Tx have caused severe shortages of donor liver organs [ 12 ]. Data on different preservation strategies suggest that MP is superior to SCS in improving short-term outcomes after human liver Tx, with a less clear effect in the longer term [ 12 ].…”

“…Rapidly increasing demands for liver Tx have caused severe shortages of donor liver organs [ 12 ]. Data on different preservation strategies suggest that MP is superior to SCS in improving short-term outcomes after human liver Tx, with a less clear effect in the longer term [ 12 ]. The use of metabolomics during liver preservation shows promising results in developing objective and reliable techniques to metabolically profile liver grafts and find reliable prognostic biomarkers prior to Tx ( Table 4 ).…”

“…The implementation of new storage techniques, such as machine perfusion (MP), has paved the way for the continuous supply of oxygen and substrates for the synthesis of adenosine triphosphate (ATP) and other metabolites, enabling the continuous removal of end products and stimulation of the organ’s metabolism [ 9 ]. Studies have demonstrated reduced rates of DGF and improved allograft survival in machine-perfused organs compared to static cold storage (SCS) [ 4 , 10 , 11 , 12 ]. Moreover, MP provides a unique opportunity to collect graft tissue and perfusate samples, as well as information regarding functional activity and flow dynamics prior to Tx.…”