虚血フリー肝移植はHNF4α-凝固因子軸を介して凝固機能を保護する：IFLT-DBDランダム化比較試験の事後解析
Yuqi Dong1,2,3,4, Xiaoxiang Chen4, Wei Xiong4
1Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
Background:
The liver is essential for coagulation-anticoagulation balance. Ischemia-free liver transplantation (IFLT) has been proven to prevent ischemia-reperfusion injury (IRI) and improve postoperative recovery. In this study, we explored protective effects of IFLT on the coagulation system.
Materials And Methods:
Sixty-five liver transplant patients were enrolled in this post hoc analysis of the IFLT-DBD (ischemia-free transplantation of livers from donors after brain death) trial. Data of blood loss, blood product transfusion, intraoperative conventional coagulation tests, and rapid thromboelastography were evaluated. Transcriptome analysis was performed, and liver tissue specimens were collected for experimental validation.
Results:
Total blood loss was significantly lower in the IFLT group than in the conventional liver transplantation (CLT) group [1765.0 (565.0-2965.0) vs 2600.0 (595.0-4605.0) mL, P<0.001]. The IFLT group had fewer red blood cells (RBC), fresh frozen plasma (FFP), and platelet (PLT) transfusions than the CLT group [RBC: 4 (2-6) vs 7.25 (2.25-8) units, P = 0.026; FFP: 600 (0-600) vs 600 (400-987.5) ml, P = 0.031; PLT: 6(18.8%) vs 13(39.4%), P = 0.026]. Bulk transcriptome analysis showed that hepatocyte nuclear factor 4 alpha (HNF4α) expression was higher in the IFLT group. Real-time PCR revealed higher mRNA expression of HNF4α, factor II, and V in the IFLT group. Western blotting showed higher HNF4α protein expression in the IFLT group.
Conclusion:
Adopting IFLT significantly decreased intraoperative hemorrhage and blood product transfusion. IFLT facilitates the restoration of intraoperative coagulation homeostasis by preserving the HNF4α-mediated regulation of hepatic coagulation factor synthesis.
