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Letter to the Editor

Ex Vivo Liver Splitting and Hypothermic Oxygenated Machine Perfusion: Technical Refinements of a Promising Preservation Strategy in Split Liver Transplantation

Mabrut, Jean-Yves MD, PhD1,2; Lesurtel, Mickaël MD, PhD1,2; Muller, Xavier MD1,2; Dubois, Rémi MD3; Ducerf, Christian MD, PhD1; Rossignol, Guillaume MD2,3; Mohkam, Kayvan MD, PhD1,2,3

Author Information
doi: 10.1097/TP.0000000000003775
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Split liver transplantation (LT) has been developed to increase organ availability, but it results in prolonged cold ischemia and higher risks of postreperfusion bleeding and ischemia-reperfusion injury (IRI). Therefore, partial liver grafts are considered as marginal grafts. Dynamic preservation strategies have been proposed to minimize IRI and optimize post-LT outcomes, especially for extended criteria donor livers; however, all current trials assessing liver machine perfusion exclude partial grafts.1 For instance, our team is currently conducting a multicenter randomized trial assessing end-ischemic hypothermic oxygenated perfusion (HOPE) before LT with extended criteria donor grafts (NCT03929523), with the exclusion of partial grafts.

We herein report an original 2-step technique of ex vivo left lateral/right extended graft splitting with concurrent HOPE: first, vessel dissection and hilar plate division are facilitated by the “star exposure” and performed during static cold storage; second, parenchymal transection is performed with simultaneous HOPE using a “split hanging maneuver” (Figure 1). After approval by the institutional ethics committee (CSE-HCL_21_202), we applied this novel approach for 2 livers, allowing us to successfully transplant 2 adults (aged 56 and 45 y) and 2 pediatric recipients (aged 36 and 5 mo, weighting 15 and 5 kg, respectively). All 4 recipients showed satisfactory allograft function recovery. The 36-mo-old child had a history of previous LT for Alagille syndrome, which complicated with hepatic artery thrombosis and ischemic cholangiopathy. He was retransplanted using the present technique in a context of marked hemodynamic instability; despite 2 relaparotomies for postoperative hemorrhage, he recovered and normalized factor V on posttransplant day 6. The 3 other recipients normalized their factor V between posttransplant day 1 and 3, which is quite remarkable compared to our experience of ex vivo split LT without HOPE.

Ex vivo 2-step split technique with simultaneous transection and perfusion using hypothermic oxygenated perfusion (HOPE). The venous ligament (VL) is divided to allow identification and dissection of the left hepatic vein (A). The hepatoduodenal ligament is dissected until identification of the portal vein (PV) and hepatic artery division branches. Dissection of the left portal vein (LPV) is performed backward to the portal bifurcation, allowing division of S1 and S4 branches. The right hepatic artery (RHA) is divided at its origin, leaving the left hepatic artery (LHA) in continuity with the full arterial axis to the left lateral graft. Sharp transection of the hilar plate is performed before parenchymal transection and guided by bench cholangiography to obtain a single bile duct for the left graft. This step is facilitated by the “star exposure,” which consists of the exposure of the following anatomical structures in a clockwise direction: the ligamentum teres, the LHA, the VL, the main PV, and the right Glissonean pedicle (including the RHA and the right PV [B]). Both grafts are then perfused with HOPE using the Liver Assist perfusion device (Organ Assist, The Netherlands) and a single portal perfusion via a 25F cannula under a 4 mm Hg pressure and a 150 mL/min portal flow at 10 °C. The vena cava is left open to allow free drainage into the organ reservoir. Parenchymal transection is then performed with simultaneous HOPE in 2 steps with an integrated bipolar/ultrasonic device (Thunderbeat, Olympus) and Prolene 5/0 stitches. A caudate approach is used to divide the left lateral graft from segment 1 and inferior part of S4 (C). After turning the graft upside down into the reservoir without interrupting portal perfusion, transection of S4 is carried out along the right side of the falciform ligament until the left hepatic vein, using an anterior approach. This step is facilitated by a “split hanging maneuver,” which allows raising the liver and offers 2 technical advantages: first, a better identification of the transection plane and, second, avoidance of an insufficient portal perfusion flow caused by graft compression (D). Finally, the left hepatic vein is divided, and the defect on the vena cava is closed (arrow) with a transverse running suture or a venous patch to avoid any stricture of the middle hepatic vein (E). The 2 grafts remain perfused by the main portal trunk as long as necessary, until hepatectomies in both recipients are carried out (F). Division of the LPV is performed as soon as 1 of the recipients is ready for graft implantation, possibly leaving the other graft perfused if necessary. Times from donor cold flush to start of back bench were 250 and 266 min, times from back bench to initiation of HOPE were 102 and 87 min, and times from initiation of HOPE to completion of parenchymal transection were 75 and 62 min, respectively. Total cold ischemia times (including HOPE) were 543 and 448 min for the 2 adult recipients and 640 and 520 min for the 2 pediatric recipients.

Ex vivo splitting with concurrent dynamic preservation represents a technical challenge, with very limited data available. Its feasibility has been suggested on discarded livers with normothermic perfusion,2,3 on swine using dual hypothermic perfusion,4 and during dual-HOPE.5,6 We herein report the 2 first cases of LT using concurrent liver splitting and HOPE through the portal vein only, which, according to us, represents the least demanding and most secure machine perfusion modality for ex vivo splitting. The graft is preserved in the cold during the entire procedure, which reduces the risk of warm ischemia due to technical problems or cannula kinking. In comparison with the report by Thorne et al,6 who perfused the graft in a supine position during both vascular dissection and parenchymal transection, our 2-step technique has the advantage of allowing bench top cholangiography, which is not currently possible after initiation of HOPE. Moreover, the split hanging maneuver in prone position allows performing parenchymal transection through an anterior approach, similarly to elective hepatectomies.

Of note, single perfusion through the portal vein facilitates the procedure and avoids arterial injury during graft handling, without compromising the protective effect of HOPE against IRI. This strategy allows to extend perfusion of both partial grafts through a single portal cannula, for example in case of a difficult recipient hepatectomy. Finally, although sequential perfusion of the 2 grafts after splitting may be easier, simultaneous splitting and perfusion enable the performance of parenchymal transection during HOPE, which hereby reduces graft rewarming caused by graft mobilization out of ice and heat exposure by the energy transection device. Further studies are needed to assess this promising dynamic preservation strategy, which may improve the outcome of split LT.


1. Muller X, Mohkam K, Mueller M, et al. Hypothermic oxygenated perfusion versus normothermic regional perfusion in liver transplantation from controlled donation after circulatory death: first international comparative study. Ann Surg. 2020;272:751–758.
2. Brockmann JG, Vogel T, Coussios C, et al. Liver splitting during normothermic organ preservation. Liver Transpl. 2017;23:701–706.
3. Stephenson BTF, Bonney GK, Laing RW, et al. Proof of concept: liver splitting during normothermic machine perfusion. J Surg Case Rep. 2018;2018:rjx218.
4. Ishii D, Matsuno N, Gochi M, et al. Applicability of hypothermic oxygenate machine perfusion preservation for split-liver transplantation in a porcine model: an experimental study. Ann Transplant. 2020;25:e919920.
5. Spada M, Angelico R, Grimaldi C, et al. The new horizon of split-liver transplantation: ex situ liver splitting during hypothermic oxygenated machine perfusion. Liver Transpl. 2020;26:1363–1367.
6. Thorne AM, Lantinga V, Bodewes S, et al. Ex situ dual hypothermic oxygenated machine perfusion for human split liver transplantation. Transplant Direct. 2021;7:e666.
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