Impact of Hypothermic Oxygenated Machine Perfusion on Hepatocellular Carcinoma Recurrence after Liver Transplantation

Abstract

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). Results: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. Conclusions: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC.

Oncologic Outcomes of Interventions to Decrease Allograft Ischemia-Reperfusion Injury within Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review

“…Overall, 938 patients who underwent LT for HCC were analysed, with 239 receiving an intervention to reduce IRI on the hepatic allograft before the surgical procedure. The Milan criteria were adopted to determine patient eligibility for LT in three of the included studies, although one study (Rigo 2023) adopted the Metro ticket 2.0 [ 17 ]. The Model for End-Stage Liver Disease (MELD) score was utilised as a prognostic score by three studies, while Kornberg et al (2015) adopted the Child–Pugh classification [ 14 ].…”

“…The utilisation of HMP was reported by two studies, each with some differences. Both Mueller et al (2020) and Rigo et al (2023) described the adoption of static cold storage before machine perfusion [ 15 , 17 ]. However, Mueller et al (2023) employed hypothermic oxygenated perfusion (HOPE), while Rigo et al (2023) used dual-hypothermic oxygenated machine perfusion (D-HOPE) [ 15 , 17 ].…”

“…Both Mueller et al (2020) and Rigo et al (2023) described the adoption of static cold storage before machine perfusion [ 15 , 17 ]. However, Mueller et al (2023) employed hypothermic oxygenated perfusion (HOPE), while Rigo et al (2023) used dual-hypothermic oxygenated machine perfusion (D-HOPE) [ 15 , 17 ]. Mueller reported no information regarding the perfusion technique (2020) [ 15 ].…”

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience

“…During hypothermic oxygenated perfusion (HOPE) highly oxygenated perfusate is distributed to re-activate aerobic mitochondrial metabolism and metabolize accumulated succinate and NADH during ischaemia to prevent later reactive oxygen species (ROS) released at normothermic reperfusion on a device or at implantation 43 . One recent study by Rigo et al 44 demonstrated the protection of candidates transplanted for HCC by hypothermic oxygenated perfusion (HOPE), specifically allowing for the use of extended-criteria donor (ECD) grafts without increasing the risk of HCC recurrence. Further, Mueller et al 45 showed a reduced risk of HCC recurrence with HOPE, again highlighting potential benefits of ex-situ perfusion in HCC cases.…”

Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future

“…The results indicated that D-HOPE did not lower HCC recurrence rates but did allow for the use of livers from extended criteria donors, potentially expanding LT access for HCC patients. 158 Conversely, a United Kingdom and Switzerland-based comparison by Mueller et al found a four-times higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70) compared to DCD livers treated with HOPE (5.7%, 4/70). 159 Similar findings were reported at an external center with more patients meeting the criteria.…”