Ex Situ Dual Hypothermic Oxygenated Machine Perfusion for Human Split Liver Transplantation

Abstract

Background. Liver splitting allows the opportunity to share a deceased graft between 2 recipients but remains underutilized. We hypothesized that liver splitting during continuous dual hypothermic oxygenated machine perfusion (DHOPE) is feasible, with shortened total cold ischemia times and improved logistics. Here, we describe a left lateral segment (LLS) and extended right lobe (ERL) liver split procedure during continuous DHOPE preservation with subsequent transplantation at 2 different centers. Methods. After transport using static cold storage, a 51-year-old brain death donor liver underwent end-ischemic DHOPE. During DHOPE, the donor liver was maintained <10 °C and oxygenated with a Po 2 of >106 kPa. An ex situ ERL/LLS split was performed with continuing DHOPE throughout the procedure to avoid additional ischemia time. Results. Total cold ischemia times for the LLS and ERL were 205 minutes and 468 minutes, respectively. Both partial grafts were successfully transplanted at 2 different transplant centers. Peak aspartate aminotransferase and alanine aminotransferase were 172 IU/L and 107 IU/L for the LLS graft, and 839 IU/L and 502 IU/L for the ERL graft, respectively. The recipient of the LLS experienced an episode of acute cellular rejection. The ERL transplantation was complicated by severe acute pancreatitis with jejunum perforation requiring percutaneous drainage and acute cellular rejection. No device-related adverse events were observed. Conclusions. Liver splitting during continuous DHOPE preservation is feasible, has the potential to substantially shorten cold ischemia time and may optimize transplant logistics. Therefore liver splitting with DHOPE can potentially improve utilization of split liver transplantation.

Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads

“…The introduction of dynamic strategies by using machine devices for graft conservation, such as hypothermic oxygenated perfusion (HOPE), is a promising tool to not only increase graft quality for transplantation [ 67 , 68 , 69 , 70 , 71 , 72 ] but also to make useful marginal organs that were originally discarded for transplantation [ 31 ].…”

“…For years, static preservation has been based on the principles of hypothermic and static storage; however, the limitation of oxygen supply is serious for graft survival, given that the conditions proposed for static preservation are far from physiological. The use of HOPE is very promising [ 67 , 68 , 69 , 70 , 71 , 72 ], as well as gas additives or hemoglobins such as M-101 that, combined with further HOPE, could be an alternative method to palliate the deficient oxygenation of the graft during static preservation conditions [ 46 , 47 ].…”

“…With all this in mind, we assume that new promising predictors may evaluate graft quality at the end of the cold storage/cold ischemia step such as glutamate dehydrogenase (mitochondrial damage), ALDH2 (mitochondrial function), succinate and itaconate accumulations, and flavin mononucleotide (FMN); in contrast to HOPE, succinate and itaconate metabolites have a predictive value at early oxygenation/reperfusion times, including FMN [ 24 , 25 , 26 , 27 ]. Moreover, we could logically assume that the use of a unique solution, such as IGL-2 [ 81 ], could be an efficient and interesting tool to protect graft mitochondrial machinery and avoid the cumulative damage induced by the mandatory complex processes before transplantation, including organ recovery and its earlier washout, subsequent graft cold storage, and additional washout to finally proceed with HOPE strategies [ 25 , 67 , 68 , 69 , 70 , 71 , 72 ]. Certainly, the suitable use of a unique solution such as IGL-2 would simplify the logistics of liver transplantation, including also the combination of split liver transplantation with HOPE [ 82 , 83 ].…”

Letter to the editor: Liver splitting during ex‐situ perfusion: Do not count your chickens before they are hatched…

“…The first case dates to 2020, [2] with both grafts transplanted in 2 children; both patients needed a relaparotomy (hemodynamic instability and bloody drainage). A second ESL-HOPE was reported in early 2021 by Thorne et al [2] : It was associated with 3.4 L of perioperative blood and needing a reoperation on day 3 for hematoma in the pediatric recipient and 6.2 L of perioperative blood loss in the adult recipient. Rossignol et al referred to an initial experience with 2 ESL-HOPE, with 1 left SLG recipient needing two relaparotomies for bleeding.…”

“…With not even a handful of cases done worldwide until now, ESL-HOPE is at the experimental stage. The first case dates to 2020, [2] with both grafts transplanted in 2 children; both patients needed a relaparotomy (hemodynamic instability and bloody drainage). A second ESL-HOPE was reported in early 2021 by Thorne et al [2] : It was associated with 3.4 L of perioperative blood and needing a reoperation on day 3 for hematoma in the pediatric recipient and 6.2 L of perioperative blood loss in the adult recipient.…”