Clin Mol Hepatol > Volume 30(3); 2024 > Article
Clinical and Molecular Hepatology 2024;30(3): 421-435.
doi: https://doi.org/10.3350/cmh.2024.0139
Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts
Shuai Wang1,2,3, Xiaohong Lin4, Yunhua Tang1,2,3, Yichen Liang1,2,3, Min Zhang1,2,3, Zhonghao Xie1,2,3, 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
Correspondence :  Xiaoshun He ,
Tel: +86-020-87306082, Fax: +86-020-87306082, Email: gdtrc@163.com
Weiqiang Ju ,
Tel: +86-020-87306082, Fax: +86-020-87306082, Email: weiqiangju@163.com
Maogen Chen ,
Tel: +86-020-87306082, Fax: +86-020-87306082, Email: chenmg3@mail.sysu.edu.cn
Received: February 22, 2024  Revised: March 23, 2024   Accepted: April 11, 2024
*Shuai Wang, Xiaohong Lin and Yunhua Tang contributed equally to this work.
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.
KeyWords: Marginal liver grafts; Liver transplantation; Ischemia-free liver transplantation; Static cold storage; Normothermic machine perfusion; Transplantation immunology

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