Clin Mol Hepatol.
2024 Jul;30(3):421-435. 10.3350/cmh.2024.0139.
Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts
- Wang S1,2,3
- Lin X4
- Tang Y1,2,3
- Liang Y1,2,3
- Zhang M1,2,3
- Xie Z1,2,3
- Guo Y1,2,3
- Dong Y1,2,3
- Zhao Q1,2,3
- Guo Z1,2,3
- Wang D1,2,3
- He X
1,2,3 - Ju W1,2,3
- Chen M1,2,3
- Affiliations
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- 1Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
- 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, People’s Republic of China
- 3Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, People’s Republic of China
- 4Department of Thyroid and Breast Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
- KMID: 2557393
- DOI: http://doi.org/10.3350/cmh.2024.0139
Abstract
- Background/Aims
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.
Methods
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.
Results
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).
Conclusions
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.
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