Abrogation of graft ischemia-reperfusion injury in ischemia-free liver transplantation

Zhiyong Guo; Jinghong Xu; Shanzhou Huang; Meixian Yin; Qiang Zhao; Weiqiang Ju; Dongping Wang; Ningxin Gao; Changjun Huang; Lu Yang; Maogen Chen; Zhiheng Zhang; Zebin Zhu; Linhe Wang; Caihui Zhu; Yixi Zhang; Yunhua Tang; Haitian Chen; Kunpeng Liu; Yuting Lu; Yi Ma; Anbin Hu; Yinghua Chen; Xiaofeng Zhu; Xiaoshun He

doi:10.1002/ctm2.546

Abrogation of graft ischemia-reperfusion injury in ischemia-free liver transplantation

Clin Transl Med. 2022 Apr;12(4):e546. doi: 10.1002/ctm2.546.

Authors

Zhiyong Guo^{1

2

3}, Jinghong Xu^{1

2

3}, Shanzhou Huang^{1

2

3}, Meixian Yin^{1

2

3}, Qiang Zhao^{1

2

3}, Weiqiang Ju^{1

2

3}, Dongping Wang^{1

2

3}, Ningxin Gao^{1

2

3}, Changjun Huang^{1

2

3}, Lu Yang⁴, Maogen Chen^{1

2

3}, Zhiheng Zhang^{1

2

3}, Zebin Zhu^{1

2

3}, Linhe Wang^{1

2

3}, Caihui Zhu^{1

2

3}, Yixi Zhang^{1

2

3}, Yunhua Tang^{1

2

3}, Haitian Chen^{1

2

3}, Kunpeng Liu^{1

2

3}, Yuting Lu^{1

2

3}, Yi Ma^{1

2

3}, Anbin Hu^{1

2

3}, Yinghua Chen^{1

2

3}, Xiaofeng Zhu^{1

2

3}, Xiaoshun He^{1

2

3}

Affiliations

¹ Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.
³ Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
⁴ Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Background: Ischemia-reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia-free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI.

Methods: Serum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT.

Results: Peak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that "metabolism of RNA" was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post-IFLT as they were post-CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients.

Conclusions: IFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization.

Keywords: ischemia-free liver transplantation; ischemia-reperfusion injury; metabolomics; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine Transaminase
Humans
Ischemia / pathology
Liver / blood supply
Liver / metabolism
Liver / pathology
Liver Transplantation* / methods
Reperfusion Injury* / metabolism
Reperfusion Injury* / pathology

Substances

Alanine Transaminase