| Ischemia-free liver transplantation improves the prognosis of recipients using Functioned Marginal Liver grafts |
| Shuai Wang1,2,3, Xiaohong Lin4, Yunhua Tang1,2,3, Yichen Liang1,2,3, Min Zhang1,2,3, Zhonghao Xie1,2, Yiwen Guo1,2,3, Yuqi Dong1,2,3, Qiang Zhao1,2,3, Zhiyong Guo1,2,3, Dongping Wang1,2,3, Xiaoshun He1,2,3, Weiqiang Ju1,2,3, Maogen Chen1,2,3 |
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 |
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Received: February 22, 2024 Revised: March 23, 2024 Accepted: April 11, 2024
*Shuai Wang and Xiaohong Lin contributed equally to this work. |
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| ABSTRACT |
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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, liver transplantation, IFLT, SCS, NMP, NK cells |
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