Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: First North American results

Abstract

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

“…The Group in Zurich used to monitor perfusate pO 2 , pCO 2 , and pH during perfusion under a pressure adjusted below 3 mmHg, resulting in flow rates ranging from 100 to 150 mL/min (0.13 mL/min/g liver) (69). (71). Other groups performed NMP using the Liver Assist device (Organ Assist), which is a pressure-controlled perfusion machine providing pulsatile arterial and continuous non-pulsatile portal flow via two independent rotary pump circuits perfusate generally contains 3 units of ABO compatible blood plus variable quantity of succinylated gelatin.…”

“…Indications to ex situ NMP, results and donor and recipient characteristics are quite heterogeneous. The first experiences, were performed as attempts to resuscitate very marginal grafts already discarded by most liver transplant centers (72,78) and so far, only three randomized prospective series have been reported (48,49,71). The first human liver transplant using ex situ NMP was published by the group in Birmingham in 2016 (78).…”

“…In the first 6 months after LT 4 cases of anastomotic strictures were described in the study group. Using the same technological device, two Canadian groups reported two prospective studies evaluating ten patients compared to an historical series (49,71). The first to be published was the study by the Edmonton group which considered 4 DCD and 6 DBD grafts (49).…”

Response to “Normothermic Machine Perfusion: A New World Deserving Careful Exploration”

“…In our opinion, total preservation time represents an overly cautious way to compare outcomes of cold stored versus NMP grafts, as it assumes that cumulative injury over time is similar with both modalities; this is hard for us to accept for metabolically functional livers actively producing bile ex vivo. Matching storage duration in both modalities would be difficult because livers require at least 4-6 h to stabilize during the NMP phase (3)(4)(5). Although extended NMP duration should be monitored closely in ongoing safety trials, accrued porcine and limited pilot clinical experience suggests that NMP duration is not a critical variable, especially when kept ≤24 h (4).…”

Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage—Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?

“…In contrast, normothermic ex vivo liver perfusion has recently been introduced into clinical practice investigating continuous NMP with near complete exclusion of SCS. The initial clinical studies demonstrated feasibility and safety (12,13).…”