SUPPLEMENTAL DIGITAL CONTENT (SDC) MATERIALS AND METHODS
Surgical Procedures
Liver Procurement: The rapid procurement technique described by Starzl et al. (45) was used in both groups. The choice of preservation solution depended on the preferences of the organ recovery center. A wedge biopsy was performed at the start of procurement, prior to ischemia (baseline biopsy).
LT Technique: In brief, the native liver was totally removed, with or without caval preservation and/or a temporary porto-caval shunt depending on technical needs and the surgeon’s choice. The liver graft was then implanted and reperfused after the completion of caval and portal anastomoses; the arterial anastomosis was performed after portal reperfusion.
Cold ischemia was considered as the time elapsed between devascularization in the donor and graft removal from the cold solution. Portal ischemia was considered as the time elapsed between devascularization in the donor and portal reperfusion in the recipient. Warm ischemia was considered as the period between graft removal from the cold solution and the final arterial reperfusion. Arterial warm ischemia was considered as the period between portal and arterial reperfusion. The IPo procedure per se implies six additional minutes of arterial ischemia before definitive arterial revascularization, arterial re-occlusion was applied upward the arterial reconstruction(s) in all cases. A second liver wedge biopsy was performed before the abdomen was closed (in all cases, within 2 hours of arterial reperfusion) to assess the degree of I/R injury (reperfusion biopsy).
Postoperative management
Immunosuppression: Transplanted patients received a standard immunosuppression regimen, including a calcineurin inhibitor (tacrolimus or cyclosporine), methylprednisolone
and mycophenolate mofetil; patients transplanted for hepatocellular carcinoma were switched to everolimus 4 to 8 weeks later.
Graft function tests monitoring: Serum levels of AST, ALT and bilirubin and INR (international normalized ratio) values were measured every 12 hours until postoperative day 5, daily until postoperative day 10 and every 2 days thereafter.
SUPPLEMENTAL DIGITAL CONTENT (SDC)
SUPPLEMENTAL FIGURES LEGEND
Figure S1: Postoperative median (A) and mean (B) AST peak values normalized to graft weight.
Figure S2: Postoperative liver function tests with and without ischemic postconditioning.
Median AST and ALT levels and mean INR and bilirubin levels did not differ significantly between the two groups at any time point. AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio.
Table S1. Intraoperative Data
Post-conditioning group (n = 50)
Control group (n = 50)
P
Cold ischemia, mean ± SD, min 420 ± 102 415 ± 111 0.84 Portal ischemia, mean ± SD, min 479 ± 97 471 ± 113 0.75
Warm ischemia, mean ± SD, min 120 ± 27 107 ± 20 0.005
Warm arterial ischemia, mean ± SD, min 58 ± 17 49 ± 17 0.01 Transfusions
RBC units, median (IQR) 3 (0-6) 5 (2-6) 0.23
FFP units, median (IQR) 8 (0-12) 7 (2-14) 0.31
Operating time, mean ± SD, min 549 ± 100 563 ± 109 0.51
Preservation solution
IGL-1 ®, n (%) 21 (42) 18 (36)
0.79
Celsior ®, n (%) 17 (34) 20 (40)
Other, n (%) 12 (24) 12 (24)
FFP, fresh frozen plasma; IQR, interquartile range; RBC, red blood cells; SD, standard deviation.
Table S2. Postoperative liver function blood tests.
Post-conditioning group (n = 50)
Control group (n = 50)
P
AST, median (IQR), IU/L
day 1 395 (300-940) 406 (203-740) 0.25
day 3 157 (99-247) 132 (89-245) 0.40
day 5 64 (26-136) 65 (42-102) 0.98
day 7 45 (29-82) 50 (31-69) 0.60
Peak value (within day 10) 426 (213-783) 463 (321-1008) 0.21 Peak value/graft weight, UI/L/g 0.23 (0.14-0.37) 0.33 (0.18-0.70) 0.079 ALT, median (IQR), IUL
day 1 447 (259-876) 497 (189-872) 0.82
day 3 312 (189-528) 312 (177-731) 0.92
day 5 193 (97-339) 199 (124-343) 0.68
day 7 122 (66-229) 138 (83-204) 0.44
Peak value (within day 10) 473 (320-956) 526 (228-1057) 0.92 INR, mean ± SD
day 1 2.1 ± 0.58 1.93 ± 0.64 0.17
day 3 1.5 ± 0.41 1.51 ± 0.51 0.91
day 5 1.33 ± 0.24 1.29 ± 0.30 0.51
day 7 1.28 ± 0.24 1.23 ± 0.24 0.26
Peak value (within day 10) 2.17 ± 0.6 2 ± 0.67 0.17 Factor V (% of normal), mean ± SD
day 1 54 ± 23 57 ± 25 0.47
day 3 92 ± 29 81 ± 31 0.10
day 5 100 ± 25 105 ± 28 0.44
day 7 107 ± 27 109 ± 31 0.74
Peak value (within day 10) 53 ± 21 54 ± 23 0.72
Total bilirubin, median (IQR), µmol/L
day 1 73 (40-142) 77 (43-164) 0.71
day 3 65 (26-132) 67 (36-120) 0.86
day 5 55 (24-126) 64 (36-162) 0.62
day 7 51 (24-87) 51 (27-107) 0.69
Peak value (within day 10) 121 (56-180) 105 (60-189) 0.98
ALT, alanine amino-transferase; AST, aspartate amino-transferase; INR, international normalized ratio; IQR, interquartile range; SD, standard deviation.
Table S3. Postoperative outcomes
Post-conditioning group (n = 50)
Control group (n = 50)
P
90-days mortality, n (%) 3 (6) 3 (6) 1.00
Morbidity
Complications ≥ grade IIIa, n (%) 24 (48) 30 (60) 0.31 Specific complications, n (%) 22 (44) 24 (48) 0.67
Re-operation 7 (14) 10 (20) 0.42
Vascular complications 3 (6) 7 (14) 0.18
Arterial 1 (2) 5 (10) 0.92
Portal 2 (4) 4 (8) 0.40
Outflow 0 (0) 0 (0) 1.00
Biliary complications 8 (16) 10 (20) 0.60
EGD 10 (20) 13 (26) 0.47
PNF 0 (0) 0 (0) 1.00
Acute rejection 8 (16) 8 (16) 1.00
General complications, n (%) 34 (68) 39 (78) 0.26 Temporary renal failure 18 (36) 18 (36) 1.00
Infection 21 (42) 27 (54) 0.23
Pulmonary 11 (22) 17 (34) 0.16
Other 33 (66) 29 (58) 0.55
ICU stay, median (IQR), days 8 (4-13) 8 (5-14) 0.92
Hospital stay, median (IQR), days 27 (21-44) 27 (20-40) 0.57
1-year graft survival rate (%) 90 92 1.00
Re-transplantation, n (%) 1 (2) 0 (0) 1.00
EGD, early graft dysfunction; ICU, intensive care unit; IQR, interquartile range; PNF, graft primary non function.
