406.5: Bile levels of keratin 19 from donations after circulatory death are associated with early graft dysfunction.

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Background and Objectives: Bile duct injury can occur during liver retrieval and transplantation, especially in livers from Donation After Circulatory Death (DCD). Normothermic Regional Perfusion (NRP) and post-ischemic Machine Perfusion (MP) have been demonstrated to reduce hepatic injury compared to static cold storage. This study aimed to investigate novel bile parameters for predicting early allograft dysfunction (EAD). Methods: Among 50 DCD donors undergoing NRP, 36 liver grafts underwent post-ischemic MP. Among the latter, 27 grafts were successfully transplanted. T-tube was routinely used and bile specimens were analysed up to one week post-transplant. Various biomarkers indicative of hepatic/cholangiocyte cell damage and inflammation were evaluated in bile samples from donors at the end of NRP (T0) (in both transplanted and non-transplanted liver grafts), at one day (T1) and one week (T2) after Liver Transplantation (LT). Results: At T0, biliary levels of keratin 19 (K-19), a marker for biliary and hepatic progenitor cells as well as an indicator of ductular reaction, were significantly higher (p< 0.01) in discarded [1003 (150-1413) ng/mL, median (interquartile range)] than in transplanted liver grafts [66 (69-72) ng/mL]. Similarly, bile acids were higher (p=0.03) in discarded [3312 (3209-3907) mM] than in transplanted liver grafts [2802 (2675-3185) mM], while phosphatidylcholine levels did not differ significantly. Bile K-19 levels at T1 and T2 were lower than at T0 (p< 0.001). Notably, among all measured bile parameters, only K-19 levels at T0, T1, and T2 correlated with the Early Allograft Failure Simplified Estimation (EASE) score (r= 0.55, p=0.04; r=0.79 p=0.0004; r=0.70, p=0.0039; respectively). Conclusion: This is the first analysis of K-19 in bile during NRP and within one week of LT. Early detection of bile K-19 levels in donors may identify livers at high risk for developing EAD. This study has been supported by the Tuscany Region, Bando Salute 2018, DCDNet Project.

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