An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.

Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression, in nine uncontrolled DCDs (uDCDs) and ten controlled DCDs (cDCDs). At NRP start, cDCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate-dehydrogenase-1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups while interleukin-6, hepatocyte growth factor and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis and autophagy mediators were higher in uDCDs than cDCDs. In conclusion, despite initial differences in liver damage biomarkers, uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree, revealed new potential candidate biomarkers.