Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation?
Abstract
:1. Introduction
2. What Is the Real HOPE-Effect in Solid Organ Transplantation?
3. What Do We Know from Clinical Studies with Hypothermic Liver Perfusion?
4. Where Do We Need More Evidence?
4.1. Do We Need to Perfuse through Portal Vein and Hepatic Artery?
4.2. Do We Really Need a Transportable Device for Hypothermic Perfusion?
4.3. How Much Cold Storage Time Can We Afford before Hypothermic Liver Perfusion?
4.4. Is FMN the Best Mitochondrial Parameter to Predict Liver Function?
5. Summary and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author and Year | Number and Type of Livers | Duration of Cold Storage before HOPE (min or h) | Duration of HMP (min or h) | Device Transport (Yes/No) | Type of Device | HMP through Portal Vein (PV) or Dually (D) | Main Study Findings |
---|---|---|---|---|---|---|---|
Van Rijn et al., 2021, RCT, multicenter | DCD livers, n = 78 | 6 h 11 min (IQR: 5 h 16 min–6 h 55 min) | 2 h 12 min (IQR: 2 h–2 h 33 min) | No | Liver Assist® | D | D-HOPE protects from ischemic cholangiopathy, interventions at the biliary tree and early allograft dysfunction. Same anastomotic stricture rate between D-HOPE group and cold storage control |
Patrono et al., 2020 ¶ | Extended DBD livers, macrosteatotic, n = 50 | 354 min (IQR: 299–390 min) | 122 min (IQR: 103–176 min) | No | Liver Assist® | D | Low rate of graft loss (2%, n = 1); the level of macrosteatosis correlates with the occurrence of EAD |
Ravaioli et al., 2019 | Extended DBD liver, donor age, and cold storage (n = 10) | 14.5 h (IQR: 10.8–22 h) | 2.2 h (IQR: 1–3.5 h) | No | VitaSmart® | PV | No PNF and significantly lower rate of EAD, significantly lower recipient transaminases after HOPE treatment and 100% graft survival compared to the cold storage control group |
Schlegel et al., 2019 * | DCD livers, n = 50 | 4.4 h (IQR: 3.5–5.2 h) | 2.0 h (IQR: 1.6–2.4 h) | No | Liver Assist® | PV | Less PNF, HAT and ischemic cholangiopathy result in a significantly improved five-year survival of HOPE-treated extended DCD liver grafts |
Patrono et al., 2019 ¶ | Extended DBD livers, macrosteatotic, n = 25 | 311 min ±53 (mean, SD) | 186 min ±49 (mean, SD) | No | Liver Assist® | D | Lower rate of postreperfusion syndrome, acute kidney injury grades 2–3, and lower EAD due to lower recipient transaminases |
Van Rijn et al., 2018 § | DCD livers, n = 20 | 358 min (IQR: 314–398 min) | 163 min (155–194 min) | No | Liver Assist® | D | D-HOPE treatment reduced reperfusion injury of the biliary tree and led to a better 6- and 12-month graft survival |
Kron et al., 2018 | Extended DBD (n = 1) and DCD (n = 5) livers, macrosteatotic, n = 6 | 4.7 h | 2.3 h | No | Liver Assist® | PV | HOPE treatment improves immediate liver function and reduces complications and graft loss |
Van Rijn et al., 2017 § | DCD livers, n = 10 | 395 min (346–457 min) | 126 min (123–135) | No | Liver Assist® | D | Restoration of ATP, lower transaminases and protection of the biliary tree from reperfusion injury and complications through D-HOPE |
Guarrera et al., 2015 | Extended DBD (n = 31) | 9.3 h ± 1.36 (mean, SD) | 3.8 h ± 0.9 (mean, SD) | No | Own Device | D | HMP showed significantly fewer biliary complications, less EAD and shorter hospital stay |
Dutkowski et al., 2015 * | DCD livers, n = 25 | 188 min (141–264 min) | 129 min | No | Liver Assist® | PV | HOPE protected from biliary complications and achieved similar outcomes compared to a matched DBD cohort |
Dutkowski et al., 2014 * | DCD livers, n = 8 | 141 min | 118 min | No | Liver Assist® | PV | Equal outcomes compared to standard DBD livers, normal immediate function, no biliary complications 8.5 months after LT |
Guarrera et al., 2010 | Extended DBD (n = 20) | 9.2 h ± 2.1 (mean, SD) | 4.3 h ± 0.9 | No | Own Device | D | HMP showed lower complications, lower EAD rates, and shorter hospital stay |
Research Group | Number of Centers | Design | Graft Type | Number of Total Participants | Primary Endpoint |
---|---|---|---|---|---|
Zurich (Switzerland) | 13 | Cold storage + HOPE vs. cold storage | DBD (incl. ECD, retransplant) | 170 | Complications 1-year CCI (Clavien III-V) |
Aachen (Germany) | 4 | Cold storage + HOPE vs. cold storage | DBD (incl. ECD) | 46 | Peak ALT within the first week |
New Jersey (USA) | 8 | Upfront HMP vs. cold storage | DBD (incl. ECD) | 140 | EAD within the first week |
Lyon (France) | 8 | Cold storage + HOPE vs. cold storage | DBD (incl. ECD) | 266 | EAD within the first week |
Bologna (Italy) | 1 | Cold storage + HOPE vs. cold storage | DBD (incl. ECD) | 220 | EAD and DGF within the first 30 days |
Warsaw (Poland) | 1 | Cold storage + HOPE vs. cold storage | DBD (incl. ECD) | 104 | Model for early graft dysfunction score in first 3 days |
Bergamo (Italy) | 1 | Cold storage + HOPE with and without cytokine filter | DBD (incl. ECD), DCD | 20 | Postreperfusion syndrome within 5 min after reperfusion |
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Panconesi, R.; Flores Carvalho, M.; Mueller, M.; Dutkowski, P.; Muiesan, P.; Schlegel, A. Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation? Transplantology 2021, 2, 149-161. https://doi.org/10.3390/transplantology2020015
Panconesi R, Flores Carvalho M, Mueller M, Dutkowski P, Muiesan P, Schlegel A. Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation? Transplantology. 2021; 2(2):149-161. https://doi.org/10.3390/transplantology2020015
Chicago/Turabian StylePanconesi, Rebecca, Mauricio Flores Carvalho, Matteo Mueller, Philipp Dutkowski, Paolo Muiesan, and Andrea Schlegel. 2021. "Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation?" Transplantology 2, no. 2: 149-161. https://doi.org/10.3390/transplantology2020015