Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts

• Published in: Clinical and molecular hepatology 2024-07, Vol.30 (3), p.421-435
• Main Authors: Wang, Shuai, Lin, Xiaohong, Tang, Yunhua, Liang, Yichen, Zhang, Min, Xie, Zhonghao, Guo, Yiwen, Dong, Yuqi, Zhao, Qiang, Guo, Zhiyong, Wang, Dongping, He, Xiaoshun, Ju, Weiqiang, Chen, Maogen
• Format: Article
• Language: English
• Subjects: Adult; Age; Body mass index; Female; Genes; Graft Survival; Humans; Infections; Interleukins - genetics; Interleukins - metabolism; Ischemia; ischemia-free liver transplantation; Killer Cells, Natural - metabolism; Liver - metabolism; Liver - pathology; Liver cancer; Liver cirrhosis; Liver diseases; Liver Transplantation; Liver transplants; Male; marginal liver grafts; Medical prognosis; Middle Aged; Mortality; Normal distribution; normothermic machine perfusion; Original; Prognosis; Propensity Score; Pyroptosis; static cold storage; Tissue Donors; Transcriptome; transplantation immunology; Veins & arteries
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2024.0139

The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on 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. FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). FML is a more important negative prognostic parameter than other marginal liver parameters. 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.