*Purpose: Whilst ex-situ normothermic machine perfusion (NMP) of the liver limits the ischaemic injury to the organ, benefits for biliary complications post-transplantation are not yet clear. Pharmacological enhancement of the hepatic lipid metabolism during NMP was shown to mitigate oxidative mediated inflammatory tissue damage. This study aims to assess whether this treatment improves biliary cell function and enhances its preservation during NMP.

*Methods: Eight discarded human donor livers were randomly allocated to two experimental groups: the control group and the treatment group (n=4), wherein the perfusate was supplemented with the drugs. Liver tissue, perfusate and bile were sampled systematically. Common hepatic duct biopsies (beginning and end of perfusion) were assessed for injury markers (damage to the lining epithelium, epithelial superficial/deep peribiliary glands, stromal necrosis, mural bleeding and thrombosis). Immunohistochemistry was performed for cytokeratin (CK)19, for integrity of the epithelial cells, and for cluster of differentiation (CD)31, for the endothelial cells.

*Results: The experimental groups are comparable in terms of donor type, warm and cold ischaemia time. Treated livers exhibit increased bile production (1.7[1.6-2.6]vs. 0.6[0.7-1.7]ml/h,p=0.021) and improved bile quality- bile pH (7.8[7.7-8.0]vs. 7.3[7.1-7.6],p=0.030). Histologically, at the end of the perfusion, bile ducts from the treated livers demonstrated less injury to the biliary epithelial cells (CK19+;p=0.024) and endothelial cells (CD31+;p=0.005) when compared to the controls. There is a strong correlation between the decreased activation of inflammatory cells (CD11b+) and the reduction in injuries to the biliary epithelial ([Spearman]r=0.813,p=0.042) and endothelial cells (r=0.703, p=0.05). Organs exhibiting better preserved biliary epithelial cells tend to produce higher volumes of bile (r=0.624,p=0.099), as well as better quality bile (r=0.620,p=0.100).

*Conclusions: This study suggests the possibility of pharmacological enhancement of bile duct preservation during NMP, potentially via mitigation of the inflammatory mediated injury. This finding might guide studies aiming to further improve biliary complication rates following NMP.

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