An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.
Giuseppina BastaFabio MelandroSerena BabboniSerena Del TurcoRudina NdreuFrancesco TorriCaterina MartinelliBeatrice SilvestriniAdriano PerisChiara LazzeriFabio GuarracinoRiccardo MorgantiPaolo MaremmaniPietro BertiniPaolo De SimoneDavide GhinolfiPublished in: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (2023)
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.
Keyphrases
- oxidative stress
- gene expression
- growth factor
- ischemia reperfusion injury
- stem cells
- dna methylation
- endoplasmic reticulum stress
- cell death
- transcription factor
- blood pressure
- poor prognosis
- clinical trial
- extracorporeal membrane oxygenation
- single cell
- cell therapy
- cell proliferation
- study protocol
- high resolution
- contrast enhanced
- bone marrow