Background: Bile production during machine perfusion and after transplantation has been used as marker of liver allograft viability and function. This study aimed to assess bile volume, composition and gene regulation when SNMP and CS were compared. Methods: Swine liver allografts were preserved for 9 hours with either SNMP combined with a hemoglobin-based oxygen carrier (HBOC) solution (n=6) or CS (n=6) and transplanted into unmatched recipients. The common bile duct was exteriorized by a biliary drain to allow bile collection post-operatively. Perfusate and bile samples were assessed for metabolomics (600 analytes). Liver biopsies were obtained and analyzed with microarray assays to assess 25,000 hepatic genes. Results: SNMP livers produced a significantly (p<0.05) higher amount of bile post-operatively. Bile acid conjugation was significantly reduced in the CS livers, which was characterized by significantly lower levels of the cysteine-derived amino acids: taurine (p<0.001) and hypotaurine (p<0.001) levels. SNMP livers showed constant clearance of bile acids from the perfusate: glycochenodeoxycholate (p=0.01) and glycohyodeoxycholic acid (p=0.002). In the first 24hrs post-transplant, recipients of CS livers produced low volumes of bile composed of hydrophobic bile salts and their byproducts: taurolithocholate (p=0.03), glycocholenate sulfate (p=0.01) taurocholenate sulfate (p=0.04). SNMP livers produced higher bile volume composed of hydrophilic bile salts: glycohyocholate, and glycochenodeoxycholate (p=0.02). Bile sterol precursors were remarkably higher in SNMP livers: lathosterol (↑3folds, p=0.001) and cholesterol (↑1.4folds, p=0.004). Fluid phase markers [mannitol (↑10folds, p=0.01) and sucrose (↑4folds, p=0.002)] were abundant in the bile of SNMP group. In contrast, bile produced by CS livers showed very high levels of allantoin (p=0.004) and 2-aminoadipate (p=0.02) metabolites, suggesting higher oxidative stress. Regulatory genes involved in the bile acid and lipid synthesis were significantly upregulated in the SNMP livers. Conclusion: Liver allografts preserved by the SNMP/HBOC system produced a significantly higher volume of bile, with higher conjugation and increased sterol components. SNMP leads to early recovery of biliary phospholipid secretion after transplantation and protects transmembrane endocytosis of the biliary epithelial cells by providing protective hydrophilic bile salts.

CITATION INFORMATION: Banan B, Lopez R, Khan Z, Hughes C, Michalopoulos G, Fontes P. Subnormothermic Machine Perfusion (SNMP) Leads to Increased Bile Production and Secretion of Hydrophilic Bile Acids After Liver Transplantation When Compared to Cold Storage (CS). Am J Transplant. 2016;16 (suppl 3).

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