Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series

Center for Liver Disease and Transplantation, Department of Surgery, Columbia University Medical Center, New York, NY, USA.
American Journal of Transplantation (Impact Factor: 6.19). 12/2009; 10(2):372-81. DOI: 10.1111/j.1600-6143.2009.02932.x
Source: PubMed

ABSTRACT Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

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    ABSTRACT: Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used to preserve kidneys for transplantation with improved results over static cold storage (SCS). At our center, we have used HMP in 31 adults receiving extended criteria donor (ECD) livers declined by the originating United Network for Organ Sharing region (“orphan livers”). These cases were compared to ECD SCS cases in a matched cohort study design. Livers were matched for donor age, recipient age, cold ischemic time, donor risk index and Model for End-Stage Liver Disease (MELD) score. HMP was performed for 3–7 h at 4–8°C using our previously published protocol. Early allograft dysfunction rates were 19% in the HMP group versus 30% in the control group (p = 0.384). One-year patient survival was 84% in the HMP group versus 80% in the SCS group (p = NS). Post hoc analysis revealed significantly less biliary complications in the HMP group versus the SCS group (4 vs. 13, p = 0.016). Mean hospital stay was significantly shorter in the HMP group (13.64 ± 10.9 vs. 20.14 ± 11.12 days in the SCS group, p = 0.001). HMP provided safe and reliable preservation in orphan livers transplanted at our center.
    American Journal of Transplantation 12/2014; 15(1). DOI:10.1111/ajt.12958 · 6.19 Impact Factor
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    ABSTRACT: The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion (MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures (hypothermia at 4 °C, normothermia at 37 °C and subnormothermia at 20 °C-25 °C). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the "state of the art" and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.
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    ABSTRACT: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. In this study, we correlated hypoxia inducible factor (HIF)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 °C. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; pH of the perfusate was also evaluated; HIF-1α mRNA and protein expression were analyzed by real time-polymerase chain reaction and ELISA, respectively. Livers perfused at 10 and 20 °C showed no difference in lactate dehydrogenase release after 6 h of perfusion (0.96 ± 0.23 vs 0.93 ± 0.09 mU/min per g) and had lower hepatic damage as compared to 30 and 37 °C (5.63 ± 0.76 vs 527.69 ± 45.27 mU/min per g, respectively, Ps < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 °C than in livers perfused at 30 and 37 °C (0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, Ps < 0.01). No sign of hypoxia was observed at 10 and 20 °C, as highlighted by low lactate release respect to livers perfused at 30 and 37 °C (121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/mL, respectively, Ps < 0.02), and low relative HIF-1α mRNA (0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, Ps < 0.05) and protein (3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, Ps < 0.05) expression. Livers perfused at 10 and 20 °C show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 °C.