A Short Period of Oxygenated Hypothermic Machine Perfusion Prior to Normothermic Machine Perfusion Improves Bile Output and Bile Composition of Extended Criteria Donor Livers


A.P.M. Matton, Y. de Vries, R. van Rijn, A.C. Westerkamp, L.C. Burlage, N. Karimian, A.S.H. Gouw, T. Lisman, R.J. Porte

Chair(s): dr. Robert A. Pol, vaat-en transplantatiechirurg, UMC Groningen & dr. Wojaiech G. Polak, chirurg, Erasmus MC

Thursday 10 march 2016

9:40 - 9:50h at Zaal 5 & 6

Categories: Parallelsessie (klinisch)

Parallel session: Parallelsessie VIII - Klinisch chirurgisch en acuut

Introduction:
A short period of end-ischemic oxygenated hypothermic machine perfusion (HMP) can restore cellular adenosine triphosphate (ATP) energy stores in donor livers prior to transplantation. Hepatic bile production is highly dependent on transmembrane ATP-binding cassette (ABC) transporters in both hepatocytes and cholangiocytes. Given the significant arterial supply of oxygen to cholangiocytes and the central role of ATP in bile production, HMP was hypothesized to improve the quantity and quality of bile produced by donor livers after subsequent normothermic reperfusion.

Methods:
Eighteen human donor livers declined for transplantation were preserved with static cold storage (median 8.1 hrs). Six of these livers underwent 2 hours of oxygenated HMP, followed by ex vivo functional assessment during 6 hours of normothermic machine perfusion (NMP). Controls were 12 livers that underwent functional assessment during 6 hours NMP without first undergoing oxygenated HMP. Bile volume and composition, as well as gene expression of relevant ABC transporters (BSEP, MDR3, CYP7A1, AE2 and CFTR) were compared.

Results:
Cumulative bile production during NMP was significantly higher in HMP preserved livers, compared to controls (at 6 hrs NMP: 33.8 vs. 8.2 ml/kg liver; p=0.019). Biliary secretion of bile salts, phospholipids and bicarbonate during NMP was higher in the HMP group, compared to controls (bile salts: 0.060 vs. 0.003 mmol/kg liver, p=0.052; phospholipids: 0.019 vs. 0.003 mmol/kg liver, p=0.053; bicarbonate during last 30 min: 477 vs. 175 mmol/kg/30 min liver, p=0.089). There were no differences in gene expression of the ABC transporters between groups.

Conclusion:
A short period of 2 hours oxygenated HMP after conventional static cold storage results in significantly higher bile output and increased biliary secretion of bile salts, phospholipids and bicarbonate after subsequent warm reperfusion. This enhanced secretory function is likely explained by increased function of the ATP-dependent bile transporters.