Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?
Abstract
:1. Introduction
2. Mechanisms of Ischemia-Reperfusion Injury
3. Specific Mechanisms of Cancer Recurrence after Liver Transplantation
3.1. The Contribution of Mitochondria
3.2. The Complex Interplay between Liver Micro-Environment and Immune System
4. Risk Factors for Liver Cancer Recurrence after Transplantation
5. Strategies with the Potential to Reduce Cancer Recurrence
5.1. Pharmacological Agents
5.2. Tailored Immunosuppression
5.3. Surgical Interventions
5.4. The Role of Organ Preservation Strategies
6. The Impact of Machine Liver Perfusion on Tumor Recurrence
7. What Is the Potential Impact of IRI on the Recurrence of Other Liver Tumors and Metastases?
8. Summary and Future Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Data Source | Country | Number of Patients | Donor Type | Preservation | Donor Risk Factors | Recipient Risk Factors | IRI Factors | Outcomes |
---|---|---|---|---|---|---|---|---|---|
Croome 2013 [68] | UNOS | USA | 5638 vs. 242 | DBD vs. DCD | SCS | dWIT, CIT | Age, MELD | NA | DCD liver recipients have a higher HCC recurrence risk compared to DBD recipients; livers with a dWIT of >15 min or a CIT of >6 h 20 min had lower survival rates |
Croome 2015 [69] | Single center | USA | 340 vs. 57 | DBD vs. DCD | SCS | CIT, dWIT (DCD) | AFP, underlying disease severity | NA | HCC recurrence in 12.1% and 12.3% in DBD and DCD liver transplants; good DCD livers have a similar risk of HCC recurrence compared to standard DBD liver recipients |
Kornberg 2015 [57] | Single | Germany | 106 | DBD | SCS(+/− Prostaglandin) | CIT, dWIT | HCC factors | AST/ALT | Up to 23.6% HCC recurrence; prolonged CIT and recipient WIT had higher HCC recurrence. The protective effect of prostaglandin on recurrence-free survival and HCC recurrence more pronounced in recipients outside the Milan criteria |
Nagai 2015 [56] | Multi-center | USA | 391 | DBD | SCS | CIT | WIT, HCC burden, AFP | AST/ALT | 15.3% overall recurrence; CIT >10 h and recipient WIT >50 min associated with higher HCC recurrence |
Orci 2015 [61] | UNOS | USA | 9206 vs. 518 | DBD vs. DCD | SCS | dWIT, age, BMI | NA | NA | Donor age >60 y and dWIT were risk factors for increased HCC recurrence |
Khorsandi 2015 [70] | Single | UK | 256 vs. 91 | DBD vs. DCD | SCS | dWIT, CIT | HCC burden | AST, INR | Recipients of good quality DCD livers have similar HCC recurrence risk compared to DBD |
Grat 2018 [73] | Single | Poland | 195 | DBD | SCS | CIT | WIT | AST, LDH, GGT, bilirubin peak, INR | AST ≥1896 U/L increases the risk of HCC recurrence, already in recipients within the Milan criteria |
Martinez- Insfran 2019 [71] | Single | Spain | 18 vs. 18 | DBD vs. DCD | SCS | CIT, dWIT | NA | AST, ALT, prothrombin time | Low risk DCD grafts can be used for standard HCC recipient, with the same recurrence rate compared with transplantation of DBD livers |
Silverstein 2020 [8] | UNOS | USA | 6996 vs. 567 | DBD vs. DCD | SCS | Organ type, dWIT, age, DRI | MELD | NA | Recurrence at 3 y: 7.6% in DCD and 6.4% in DBD livers; DCD livers were an independent predictor of mortality. Donor or graft quality and HCC parameters impact on outcomes |
Study | Study Type | Country | Number of Patients | Donor Type | Preservation | Donor Risk Factors | Recipient Risk Factors | IRI Factors | Outcomes | Discussion |
---|---|---|---|---|---|---|---|---|---|---|
Mueller 2020 [136] | Multi-center, matched retrospective | UK, Switzerland | 70 vs. 70 | DBD vs. DCD | HOPE (DCD) vs. SCS (DBD) | Preservation type | HCC burden (DCD HOPE group: 35.7% outside Milan, 28.6% outside UCSF, 18.6% outside Metro-ticket 2.0) | ALT, INR, CRP | HOPE-treated DCD liver recipients had a 5-year tumor-free survival of 92%. 4-fold higher tumor recurrence rate was seen in recipients of unperfused DBD livers compared to DCD grafts with HOPE (25.7% vs. 5.7%, p = 0.002) | Retrospective |
Tang 2021 [137] | Single center, matched retrospective | China | 85 vs. 30 | DBD | SCS vs. IFOT | Preservation type | AFP, microvascular invasion | AST, ALT, lactate | Higher recurrence-free survival with IFOT; 1 and 3 y: 92% and 87% IFOT vs. 88% and 53.6% with SCS | Retrospective |
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Parente, A.; Flores Carvalho, M.; Eden, J.; Dutkowski, P.; Schlegel, A. Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion? Int. J. Mol. Sci. 2022, 23, 9747. https://doi.org/10.3390/ijms23179747
Parente A, Flores Carvalho M, Eden J, Dutkowski P, Schlegel A. Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion? International Journal of Molecular Sciences. 2022; 23(17):9747. https://doi.org/10.3390/ijms23179747
Chicago/Turabian StyleParente, Alessandro, Mauricio Flores Carvalho, Janina Eden, Philipp Dutkowski, and Andrea Schlegel. 2022. "Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?" International Journal of Molecular Sciences 23, no. 17: 9747. https://doi.org/10.3390/ijms23179747