Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma

Abstract

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation. Liver Transplantation 26 215-226 2020 AASLD.Among the strategies employed to improve liver allograft utilization, ex situ normothermic machine perfusion (NMP) preservation has drawn increasing interest in the last decade. The potential advantage of this technology over static cold storage is the ability to enhance preservation along with the capacity to assess and improve graft viability. This is of particular importance when considering organs from extended criteria donors. (1) The type of perfusion solution plays a critical role in the success of NMP. Clinical studies in ex situ preservation have employed packed red blood cells (PRBCs) as oxygen carriers in combination with a colloid extracellular solution (Gelofusine, B Braun, Melsungen, Germany), (2)(3)(4) Steen solution (Gelofusine, B Braun), (5) and 5% albumin (6)(7)(8) ). Fresh frozen plasma (FFP), the most physiological of all extracellular fluids, has never been tested liu et al.

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

“…Briefly, Initial literature searches identified 1,289 publications. After excluding ineligible publications based on the selection and exclusion criteria, 12 studies, including 10 nonrandomized prospective phase I clinical trials (10,(21)(22)(23)(24)(25)(26)(27)(28)(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 MP and 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).…”

“…As shown in Table 2, all 12 included studies reported posttransplant peak ALT and/or AST level within 1 week. Seven of the 12 included studies found a significantly lower posttransplant peak ALT and/or AST level during the first 7 days after surgery in the MP group compared with the CS group (P < 0.05) (10,18,21,22,25,26,28), whereas the rest (five studies) observed comparable hepatic transaminases levels between two groups (23,24,27,29,30). However, different studies reported transaminase by different data types and at variable time points.…”

Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

“…To do this, NMP requires the use of oxygenators and the presence of oxygen transporters in the perfusate, with human red blood cells being the most common oxygen transporter used in current protocols. [45][46][47][48][49][50] Unlike the HMP configuration, in NMP protocols, liver grafts are normally dually perfused through the portal vein and the hepatic artery. The maintenance of the organ metabolic activity during NMP offers the possibility to assess organ viability by measuring many metabolic parameters, such as lactate clearance, pH and glycemic levels, as well as bile production and its constitution.…”

“…Using a noncommercial custom-made perfusion device, Liu et al compared the outcome of 21 LT performed with NMP-preserved livers to a historical series of LT performed with livers preserved by SCS in a 1:4 ratio. The NMP group presented less EAD, no cases of biliary complications, and the only death in this group was due to a cerebral vascular accident 8 months after LT. 50 Recently, Jassem et al reanalyzed liver tissue samples and hepatic mononuclear cells collected from DBD livers transplanted after NMP and initially published by Ravikumar et al They observed that NMP changed the gene expression profile from proinflammation to prohealing and regeneration compared with SCS liver samples. In addition, they observed a reduction in the population of T cells that produce inflammatory factors and an increase in the pool of regulatory T cells in NMP livers.…”

“…In two studies, there was a period of initial SCS approximately 4 hours prior to NMP. 49,50 Red blood cells were the oxygen transporter in all the mentioned studies in association with either Gelofusine or FFP or Steen solution.…”