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

作者：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 · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.546 · 被引用次数：45 · 研究领域：Organ Transplantation Techniques and Outcomes、Liver Disease and Transplantation、Renal Transplantation Outcomes and Treatments

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 w...