Evidence-based improvements in liver transplantation outcomes

Bral M, Dajani K, Leon Izquierdo D et al. Liver Transpl. 2019;25:848–58.

A nonrandomised pilot study assessing whether the OrganOx metra can be used with a back-to-base model without impacting patient outcomes.

Manzia TM, Toti L, Quaranta C, et al. Int J Surg Rep. 2019;57:163–6.

This case report details how functional assessment of a nonagenarian liver with the OrganOx metra resulted in successful transplantation.

Robinson, T., Vargas, P. A., Yemini, R., Goldaracena, N., & Pelletier, S. (2024). Are we on track to increase organ utilization? An analysis of machine perfusion preservation for liver transplantation in the United States. Artificial Organs. https://doi.org/10.1111/aor.14812 

UNOS database analysis showing that NMP was associated with less liver non-utilization, particularly ECD livers which had comparable outcomes to standard criteria livers if they underwent NMP.

Watson, C. J. E., MacDonald, S., Bridgeman, C., Brais, R., Upponi, S. S., Foukaneli, T., Swift, L., Fear, C., Selves, L., Kosmoliaptsis, V., Allison, M., Hogg, R., Saeb Parsy, K., Thomas, W., Gaurav, R., & Butler, A. J. (2023). D-dimer release from livers during ex situ normothermic perfusion and after in situ normothermic regional perfusion: Evidence for occult fibrin burden associated with adverse transplant outcomes and cholangiopathy. Transplantation, 107(11), 2019-2029.

Demonstration of the presence of d-dimers in the perfusate of DBD and DCD livers undergoing perfusion. High levels were associated with graft failure and cholangiopathy. (D-dimers are breakdown products of fibrin). Supports theory that intravascular fibrin is the cause of post transplant cholangiopathy.

Wehrle, C. J., Zhang, M., Khalil, M., Pita, A., Modaresi Esfeh, J., Diago-Uso, T., Kim, J., Aucejo, F., Kwon, D. C. H., Ali, K., Cazzaniga, B., Miyazaki, Y., Liu, Q., Fares, S., Hong, H., Tuul, M., Jiao, C., Sun, K., Fairchild, R. L., Quintini, C., Fujiki, M., Pinna, A. D., Miller, C., Hashimoto, K., & Schlegel, A. (2024). Impact of back-to-base normothermic machine perfusion on complications and costs: A multicenter, real-world risk-matched analysis. Annals of Surgery, 280(2), 300-310.

US cost analysis of end-ischemic NMP using the metra compared to SCS livers based on results from 2 centers. While organ recovery costs were more with NMP, overall healthcare costs were similar due to the reduction in complications seen with the metra.

Qureshi, S., Elliott, H., Noel, A., Swift, L., Fear, C., Webster, R., Brown, N. M., Gaurav, R., Butler, A. J., & Watson, C. J. E. (2024). Infection and prophylaxis during normothermic liver perfusion: Audit of incidence and pharmacokinetics of antimicrobial therapy. Transplantation, 108(6), 1376-1382.

Review of 210 metra perfusions and the microorganisms cultured. Also demonstrates drug levels of meropenem and fluconazole in the perfusate of livers on the metra, with recommendations for antimicrobial prophylaxis.

Meszaros, A. T., Hofmann, J., Buch, M. L., Cardini, B., Dunzendorfer-Matt, T., Nardin, F., Blumer, M. J., Fodor, M., Hermann, M., Zelger, B., Otarashvili, G., Schartner, M., Weissenbacher, A., Oberhuber, R., Resch, T., Troppmair, J., Öfner, D., Zoller, H., Tilg, H., Gnaiger, E., Hautz, T., & Schneeberger, S. (2022). Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome. EBioMedicine, 85, 104311. https://doi.org/10.1016/j.ebiom.2022.104311

Study of 50 livers undergoing NMP on the metra examining integrity of mitchondrial function by serial biopsies and showing a wide variability in mitchondrial respiration at the end of cold storage, but stable levels of function during NMP. The preservation of mitchondrial respiration predicted outcome post transplant.

Chapman, W. C., Barbas, A. S., D'Alessandro, A. M., Vianna, R., Kubal, C. A., Abt, P., Sonnenday, C., Barth, R., Alvarez-Casas, J., Yersiz, H., Eckhoff, D., Cannon, R., Genyk, Y., Sher, L., Singer, A., Feng, S., Roll, G., Cohen, A., Doyle, M. B., Sudan, D. L., Al-Adra, D., Khan, A., Subramanian, V., Abraham, N., Olthoff, K., Tekin, A., Berg, L., Coussios, C., Morris, C., Randle, L., Friend, P., & Knechtle, S. J. (2023). Normothermic machine perfusion of donor livers for transplantation in the United States: A randomized controlled trial. Annals of Surgery, 278(5), e912-e921.

Report of the US multicentrer study of NMP comparing 191 livers preserved with SCS and 192 undergoing NMP; 136 NMP and 130 SCS livers were transplanted. NMP livers had less early allograft dysfunction (non-significant) overall, much more apparent in DCD livers where the incidence was highest in SCS livers, andsignificnatly less post reperfusion syndrome than SCS livers.

Watson, C. J. E., Gaurav, R., Fear, C., Swift, L., Selves, L., Ceresa, C. D. L., Upponi, S. S., Brais, R., Allison, M., Macdonald-Wallis, C., Taylor, R., & Butler, A. J. (2022). Predicting early allograft function after normothermic machine perfusion. Transplantation, 106(12), 2391-2398.

Multivariate analysis of 154 metra perfused livers looking at perfusate chemistry which predicts better early allograft function as measured by the Model for Early Allograft Function (MEAF) score. ALT and lactate measured at 2 hours were the biggest predictors, followed by the need for bicarbonate to maintain pH.

Webb, A. N., Izquierdo, D. L., Eurich, D. T., Shapiro, A. M. J., & Bigam, D. L. (2021). The actual operative costs of liver transplantation and normothermic machine perfusion in a Canadian setting. Pharmacoeconomics Open, 5(2), 311-318.

Canadian study detemrmining the actual cost of recovering recovering livers in and out of province as a prelude to a cost effectiveness study of NMP.

Mergental, H., Laing, R. W., Kirkham, A. J., Perera, M. T. P. R., Boteon, Y. L., Attard, J., Barton, D., Curbishley, S., Wilkhu, M., Neil, D. A. H., Hübscher, S. G., Muiesan, P., Isaac, J. R., Roberts, K. J., Abradelo, M., Schlegel, A., Ferguson, J., Cilliers, H., Bion, J., Adams, D. H., Morris, C., Friend, P. J., Yap, C., Afford, S. C., & Mirza, D. F. (2020). Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nature Communications, 11, 2939. https://doi.org/10.1038/s41467-020-16251-3

UK study of 22 livers declined by all UK centres that were assessed on the metra and transplanted, with 100% 90 day graft survival. Results were similar to a contemporay cohort of standard livers, although later follow up reported biliary complications in DCD livers reflecting study protocol not assessing bile for bile duct viability.

Reddy S, Zivetti M, Brockmann J, McClaren A and Friend PJ – Liver Transplantation (2019) 10 1223-1232.

Nasralla D, Coussios CC, Mergental H, et al. Consortium for Organ Preservation in Europe. Nature. 2018;557(7703):50–56.

The first randomised controlled trial comparing machine perfusion technology with static cold storage in human liver transplantation. In this trial, the OrganOx metra was transported to and from the donor centre to minimise cold storage time.

Compared with static cold storage, the OrganOx metra achieved a 50% lower level of graft injury despite a 50% lower rate of organ discard and a 54% longer mean preservation time.

Watson, C. J. E., Gaurav, R., Swift, L., Fear, C., Allison, M. E. D., Upponi, S. S., Brais, R., & Butler, A. J. (2024). Bile chemistry during ex situ normothermic liver perfusion does not always predict cholangiopathy. Transplantation, 108(11), 2040-2047.

Review of bile chemistry of 200 perfused livers showing what is normal chemistry and comments on assessing bile duct viability by looking at bile chemistry.

Cardini, B., Oberhuber, R., Fodor, M., Hautz, T., Margreiter, C., Resch, T., Scheidl, S., Maglione, M., Bösmüller, C., Mair, H., Frank, M., Augustin, F., Griesmacher, A., Schennach, H., Martini, J., Breitkopf, R., Eschertzhuber, S., Pajk, W., Obwegeser, A., Tilg, H., Watson, C., Öfner, D., Weissenbacher, A., & Schneeberger, S. (2020). Clinical implementation of prolonged liver preservation and monitoring through normothermic machine perfusion in liver transplantation. Transplantation, 104(9), 1917-1928. https://doi.org/10.1097/TP.0000000000003296 

Single centre report of early NMP experience where 34 livers underwent NMP, with 25 successfully transplanted. Graft and pateint survival 88% at 20 months. Preservation times up to 38h reported, and daytime surgery became routine.