Background & aims: The shortage of donor livers hinders the development of liver transplantations. This study aimed to clarify the poor outcomes of functioned marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) on transplantation with FMLs.
Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FMLs were compared to demonstrate the negative impact of FMLs in liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles.
Results: FMLs showed a significantly higher Hazard Ratio (HR: 1.969, P = 0.018) than other marginal livers. A worse 90-days survival (12.3% vs. 5.0%, P = 0.007) was observed in patients who underwent FMLs. Patients receiving FMLs had a significant overall survival benefit after IFLT (10.4% vs. 31.3%, P = 0.006). Pyroptosis and inflammation are inhibited in patients who undergo IFLT. The infiltration of Natural Killer cells was lower in liver grafts from these patients. A positive relationship was observed between IL32 and Caspase 1 (R = 0.73, P = 0.01) and Gasdermin D (R = 0.84, P = 0.0012) in the bulk transcriptome profiles.
Conclusion: FMLs function as a more important negative prognostic parameter than other marginal livers do. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.
Keywords: Functioned marginal liver; IFLT; NK cells; NMP; SCS; liver transplantation.