REFERENCES
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-63.
2. Riihimäki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765.
3. Oki E, Ando K, Nakanishi R, et al. Recent advances in treatment for colorectal liver metastasis. Ann Gastroenterol Surg. 2018;2:167-75.
4. Adam R, Kitano Y. Multidisciplinary approach of liver metastases from colorectal cancer. Ann Gastroenterol Surg. 2019;3:50-6.
5. Tatsuta K, Sakata M, Kojima T, Booka E, Kurachi K, Takeuchi H. Updated insights into the impact of adjuvant chemotherapy on recurrence and survival after curative resection of liver or lung metastases in colorectal cancer: a rapid review and meta-analysis. World J Surg Oncol. 2025;23:56.
6. Bzeizi KI, Abdullah M, Vidyasagar K, Alqahthani SA, Broering D. Hepatocellular carcinoma recurrence and mortality rate post liver transplantation: meta-analysis and systematic review of real-world evidence. Cancers. 2022;14:5114.
8. Canizares S, Montalvan A, Chumdermpadetsuk R, Modest A, Eckhoff D, Lee DD. Liver machine perfusion technology: expanding the donor pool to improve access to liver transplantation. Am J Transplant. 2024;24:1664-74.
9. Krüger M, Ruppelt A, Kappler B, et al. Normothermic ex vivo liver platform using porcine slaughterhouse livers for disease modeling. Bioengineering. 2022;9:471.
10. Raigani S, Carroll C, Griffith S, et al. Improvement of steatotic rat liver function with a defatting cocktail during ex situ normothermic machine perfusion is not directly related to liver fat content. PLoS ONE. 2020;15:e0232886.
11. Stevens LJ, van de Steeg E, Doppenberg JB, Alwayn IPJ, Knibbe CAJ, Dubbeld J. Ex vivo gut-hepato-biliary organ perfusion model to characterize oral absorption, gut-wall metabolism, pre-systemic hepatic metabolism and biliary excretion; application to midazolam. Eur J Pharm Sci. 2024;196:106760.
12. Yeganeh M, Zito A, Sadat M, Pierro A, Rogers IM. Ex vivo organ perfusion systems for disease modeling and therapeutic applications in small animal models. J Tissue Eng Regen Med. 2025:16.
13. Liew B, Nasralla D, Iype S, Pollok JM, Davidson B, Raptis DA. Liver transplant outcomes after ex vivo machine perfusion: a meta-analysis. Br J Surg. 2021;108:1409-16.
14. Nasralla D, Coussios CC, Mergental H, et al.; Consortium for Organ Preservation in Europe. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557:50-6.
15. Li J, Lu H, Zhang J, Li Y, Zhao Q. Comprehensive approach to assessment of liver viability during normothermic machine perfusion. J Clin Transl Hepatol. 2023;11:466-79.
16. Lascaris B, Woltjes LC, Bodewes SB, Porte RJ, de Meijer VE, Nijsten MWN. Metabolic balance of human livers during long-term normothermic machine perfusion. Am J Physiol Gastrointest Liver Physiol. 2025;328:G522-32.
17. Cillo U, Nalesso F, Bertacco A, Indraccolo S, Gringeri E. Normothermic perfusion of a human tumoral liver for 17 days with concomitant extracorporeal blood purification therapy: case description. J Hepatol. 2024;81:e96-8.
18. Boteon YL, Attard J, Boteon APCS, et al. Manipulation of lipid metabolism during normothermic machine perfusion: effect of defatting therapies on donor liver functional recovery. Liver Transpl. 2019;25:1007-22.
19. Nagrath D, Xu H, Tanimura Y, et al. Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo. Metab Eng. 2009;11:274-83.
20. Lee ACH, Edobor A, Lysandrou M, et al. The effect of normothermic machine perfusion on the immune profile of donor liver. Front Immunol. 2022;13:788935.
21. Hautz T, Salcher S, Fodor M, et al. Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver. Nat Commun. 2023;14:2285.
22. Hautz T, Hackl H, Gottschling H, et al. Transcriptomic signatures during normothermic liver machine perfusion correspond with graft quality and predict the early graft function. EBioMedicine. 2024;108:105330.
23. Zhang Y, Cui K, Yang Y, et al. Infiltration of a unique CD8+CD274+ cell subgroup in hepatocellular carcinoma is associated with poor clinical outcomes. J Hepatocell Carcinoma. 2023;10:1051-67.
24. Zimmermann J, Carter AW. Cost-utility analysis of normothermic and hypothermic ex-situ machine perfusion in liver transplantation. Br J Surg. 2022;109:e31-2.
25. Maspero M, Yilmaz S, Cazzaniga B, et al. The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence. JHEP Rep. 2023;5:100846.
26. Ravaioli M, Germinario G, Dajti G, et al. Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial. Am J Transplant. 2022;22:2401-8.
27. Eden J, Brüggenwirth IMA, Berlakovich G, et al. Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study). J Hepatol. 2025;82:97-106.
28. Schlegel A, Mueller M, Muller X, et al. A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation. J Hepatol. 2023;78:783-93.
29. Jeddou H, Tzedakis S, Chaouch MA, Sulpice L, Samson M, Boudjema K. Viability assessment during normothermic machine liver perfusion: a literature review. Liver Int. 2025;45:e16244.
30. Eden J, Thorne AM, Bodewes SB, et al. Assessment of liver graft quality during hypothermic oxygenated perfusion: the first international validation study. J Hepatol. 2025;82:523-34.
31. Lurje I, Uluk D, Hammerich L, Pratschke J, Tacke F, Lurje G. Comparing hypothermic oxygenated and normothermic liver machine perfusion: Translation matters. J Hepatol. 2024;80:e163-5.
32. 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.
33. Lau NS, Ly M, Dennis C, et al. Liver splitting during normothermic machine perfusion: a novel method to combine the advantages of both in-situ and ex-vivo techniques. HPB. 2023;25:543-55.
34. Attard JA, Osei-Bordom DC, Boteon Y, et al. Ex situ normothermic split liver machine perfusion: protocol for robust comparative controls in liver function assessment suitable for evaluation of novel therapeutic interventions in the pre-clinical setting. Front Surg. 2021;8:627332.
35. Lau NS, Ly M, Dennis C, et al. Long-term ex situ normothermic perfusion of human split livers for more than 1 week. Nat Commun. 2023;14:4755.
36. Lau NS, Ly M, Dennis C, et al. Long-term normothermic perfusion of human livers for longer than 12 days. Artif Organs. 2022;46:2504-10.
37. Lau NS, Ly M, Dennis C, et al. Microbial contamination during long-term ex vivo normothermic machine perfusion of human livers. Transplantation. 2024;108:198-203.
38. Kanani T, Isherwood J, Chung WY, et al. A O03 ex vivo perfusion of isolated human liver segments: the development of a novel model for ethical, translational research. Br J Surg. 2022;109:znac404.003.
39. Kanani T, Alnabati N, Tang S, et al. HPB O04 segmental perfusion of ex-vivo human liver segments: a 3Rs compliant directly translatable model for pharmacological, bacteriological and genetic research. Br J Surg. 2023;110:znad348.018.
40. An H, Qian C, Huang Y, et al. Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria. J Exp Med. 2022;219:e20212032.
41. Ferreira GS, Veening-Griffioen DH, Boon WPC, Moors EHM, van Meer PJK. Levelling the translational gap for animal to human efficacy data. Animals. 2020;10:1199.
42. Trebo M, Maurer T, Krendl FJ, et al. Ex vivo modelling of human colorectal cancer liver metastasis by normothermic machine perfusion. Mol Cancer. 2025;24:264.
43. Krendl FJ, Cardini B, Zoller H, Schneeberger S, Oberhuber R. Leveraging normothermic liver machine perfusion as a platform for oncologic assessment in cirrhotic livers. J Hepatol. 2025;82:e12-4.
44. Clark AM, Ma B, Taylor DL, Griffith L, Wells A. Liver metastases: microenvironments and ex-vivo models. Exp Biol Med. 2016;241:1639-52.
45. Jagatia R, Doornebal EJ, Rastovic U, et al. Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing. EBioMedicine. 2023;97:104826.
46. Del Turco S, Cappello V, Tapeinos C, et al. Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: a pilot study. Liver Transpl. 2022;28:1173-85.
47. Tang JLY, Moonshi SS, Ta HT. Nanoceria: an innovative strategy for cancer treatment. Cell Mol Life Sci. 2023;80:46.
48. Liu F, Li R, Zhu Z, Yang Y, Lu F. Current developments of gene therapy in human diseases. MedComm. 2024;5:e645.
49. Cabanes-Creus M, Liao SHY, Gale Navarro R, et al. Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation. Nat Commun. 2024;15:1876.
50. Brevini T, Swift L, Reynolds H, et al. Successful AAV8 gene therapy on hepatic ex situ machine perfusion for mitochondrial neurogastrointestinal encephalomyopathy. J Hepatol. 2025;83:1218-25.
51. Tingle SJ, Thompson ER, Bates L, et al. Pharmacological testing of therapeutics using normothermic machine perfusion: a pilot study of 2,4-dinitrophenol delivery to steatotic human livers. Artif Organs. 2022;46:2201-14.
52. Mueller M, Kalisvaart M, O’Rourke J, et al. Hypothermic oxygenated liver perfusion (HOPE) prevents tumor recurrence in liver transplantation from donation after circulatory death. Ann Surg. 2020;272:759-65.
53. Dajti G, Germinario G, Prosperi E, et al. The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation. Artif Organs. 2024;48:619-25.
54. Rigo F, De Stefano N, Patrono D, et al. Impact of hypothermic oxygenated machine perfusion on hepatocellular carcinoma recurrence after liver transplantation. J Pers Med. 2023;13:703.
55. Eden J, Müller PC, Kuemmerli C, et al.; HOPE4Cancer Trial Investigators. Hypothermic oxygenated perfusion (HOPE) against cancer recurrence after liver transplantation for hepatocellular carcinoma-study protocol for an international multicenter randomized controlled trial (HOPE4Cancer). Trials. 2025;26:369.
56. Bianchi ME, Mezzapelle R. The chemokine receptor CXCR4 in cell proliferation and tissue regeneration. Front Immunol. 2020;11:2109.
57. Zhao J, Hu Z, Zheng X, et al. Blood biomarkers of hepatocellular carcinoma: a critical review. Front Cell Dev Biol. 2024;12:1489836.
58. Fan R, Papatheodoridis G, Sun J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020;73:1368-78.
59. Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular carcinoma risk scores from modeling to real clinical practice in areas highly endemic for hepatitis B infection. J Clin Transl Hepatol. 2023;11:1508-19.
60. Liu Z, Yuan H, Suo C, et al. Point-based risk score for the risk stratification and prediction of hepatocellular carcinoma: a population-based random survival forest modeling study. EClinicalMedicine. 2024;75:102796.
61. Barjasteh AH, Jaseb Mazhar AleKassar R, Al-Asady AM, et al. Therapeutic potentials of miRNA for colorectal cancer liver metastasis treatment: a narrative review. Iran J Med Sci. 2025;50:202-19.
62. Amr KS, Elmawgoud Atia HA, Elazeem Elbnhawy RA, Ezzat WM. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Dis. 2017;4:215-21.
63. Domínguez-Oliva A, Hernández-Ávalos I, Martínez-Burnes J, Olmos-Hernández A, Verduzco-Mendoza A, Mota-Rojas D. The importance of animal models in biomedical research: current insights and applications. Animals. 2023;13:1223.
64. EMA. Regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches - Scientific guideline. Available from: https://www.ema.europa.eu/en/regulatory-acceptance-3r-replacement-reduction-refinement-testing-approaches-scientific-guideline. [Last accessed on 23 Mar 2026].
65. Landi M, Everitt J, Berridge B. Bioethical, reproducibility, and translational challenges of animal models. ILAR J. 2021;62:60-5.
