Optimizing Livers for Transplantation Using Machine Perfusion versus Cold Storage in Large Animal Studies and Human Studies: A Systematic Review and Meta-Analysis

Abstract

Background Liver allograft preservation frequently involves static cold storage (CS) and machine perfusion (MP). With its increasing popularity, we investigated whether MP was superior to CS in terms of beneficial outcomes. Methods Human studies and large animal studies that optimized livers for transplantation using MP versus CS were assessed (PubMed/Medline/EMBASE). Meta-analyses were conducted for comparisons. Study quality was assessed according to the Newcastle-Ottawa quality assessment scale and SYRCLE's risk of bias tool. Results Nineteen studies were included. Among the large animal studies, lower levels of lactate dehydrogenase (SMD -3.16, 95% CI -5.14 to -1.18), alanine transferase (SMD -2.46, 95% CI -4.03 to -0.90), and hyaluronic acid (SMD -2.48, 95% CI -4.21 to -0.74) were observed in SNMP-preserved compared to CS-preserved livers. NMP-preserved livers showing lower level of hyaluronic acid (SMD -3.97, 95% CI -5.46 to -2.47) compared to CS-preserved livers. Biliary complications (RR 0.45, 95% CI 0.28 to 0.73) and early graft dysfunction (RR 0.56, 95% CI 0.34 to 0.92) also significantly reduced with HMP preservation in human studies. No evidence of publication bias was found. Conclusions MP preservation could improve short-term outcomes after transplantation compared to CS preservation. Additional randomized controlled trials (RCTs) are needed to develop clinical applications of MP preservation.

Machine Perfusions in Liver Transplantation: The Evidence‐Based Position Paper of the Italian Society of Organ and Tissue Transplantation

“…(10,14) recOMMenDatiOn We suggest the use of HMP to reduce posttransplant EAD. (2D) taBle 3. literature search and evaluation for chapter 2: nMp Quality of evidence in the selected articles regarding NMP Quality of evidence in the selected articles for meta-analysis according to AMSTAR Jiang et al (47) Moderate…”

“…To date, only 2 prospective RCTs (29,38) and 3 prospective studies (26,30,39) comparing NMP and SCS have been published, whereas other available articles were small case series or case reports. (27,28,(31)(32)(33)(34)(35)(36)(37)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52) Also, no national or international registries exist (Table 3).…”

Hospital-Based Health Technology Assessment of Machine Perfusion Systems for Human Liver Transplantation

“…In comparative studies, in light of similar rates of transplant-related (i.e., artery thrombosis) and unrelated (i.e., bleeding) complications (15,24,30,32,35,37), MP allowed for prolonged total graft preservation time (15,35), a 10%-50% reduced risk for EAD (7,17,24,30,36,37,41,47), 7%-15% less IRI (7,17,28,32,39,42), 7-50% fewer ischemic biliary complications (IBC) (7,15,17,24,30,31,36,37,47), comparable (22,24) or improved 1-year graft (30,47) and patient survival (30,35), and up to a 50% lower discard rate (31,35,43). Hospital stay was not longer for MP patients (15,24,30), and technical failures were anecdotal (36). Costs of MP have limitedly been investigated in two studies only (13,21).…”

“…• No increased complication rate (15,24,30,32,35,37) • Prolonged total graft preservation time (15,35) • 10-50% reduced risk for EAD (7,17,24,30,36,37,41,47) • 7-15% less IRI (7,17,28,32,39,42) • 7-50% fewer IBC (7,15,17,24,30,31,36,37,47) • Comparable (22,24) or improved 1-year graft (30,47) and patient survival (30,35) • Up to a 50% lower discard rate (31,35,43) Economic(al) technology. As clinicians, we are challenged to think through all these methodological issues related to MP technology and build empirical evidence in our future practice.…”

A Potential Route to Reduce Ischemia/Reperfusion Injury in Organ Preservation

“…Recently, perfusion machines have appeared on the market, which replace the simple hypothermic box and perfuse the organ with an organ preservation solution at +4 °C, in this case called machine perfusion solution (MPS). Both techniques are used in clinical practice, and in both cases, the organ is in contact with a cold solution [ 14 , 15 , 16 , 17 , 18 ].…”