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 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including & alpha;-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 IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the 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.