Original article

Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 16, Issue 4, pp 513-520

First online:

Tissue factor expression demonstrates severe sinusoidal endothelial cell damage during rejection after living-donor liver transplantation

  • Masanobu UsuiAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University Email author 
  • , Naohisa KuriyamaAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Masashi KisawadaAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Takashi HamadaAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Shugo MizunoAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Hiroyuki SakuraiAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Masami TabataAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University
  • , Hiroshi ImaiAffiliated withDepartment of Pathology, Graduate School of Medicine, Mie University
  • , Kohji OkamotoAffiliated withFirst Department of Surgery, University of Occupational and Environmental Health
    • , Shinji UemotoAffiliated withDepartment of Hepatobiliary Pancreatic and Transplantation Surgery, Graduate School of Medicine, Kyoto University
    • , Shuji IsajiAffiliated withDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University

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Abstract

Background/Purpose

Since it is well known that endothelial cells may be important targets during rejection after living-donor liver transplantation, in this study we investigated liver sinusoidal endothelial cell (SEC) damage during rejection by focusing on thrombomodulin (TM) and hyaluronic acid (HA) as plasma markers of SEC damage. We also examined tissue factor (TF) expression in SECs, because damage to endothelial cells leads to immediate activation of the coagulation system, with the damage being triggered mainly by TF.

Methods

Living-donor liver transplantation was performed at Mie University Hospital between March 2002 and December 2007; there were 8 patients with rejection (4 with acute cellular rejection and 4 with chronic rejection) and 32 patients without rejection. Liver biopsy tissue was immunostained with an anti-TF antibody, and assessed for SEC damage. In addition, total RNA was extracted from liver biopsy tissue and tested for TF mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR).

Results

The plasma TM level was significantly higher in the rejection group than in the non-rejection group. TF expression was observed in SECs, in infiltrating inflammatory cells, and in the vascular endothelium in the rejection group. TF mRNA expression was significantly higher in the rejection group than in the non-rejection group.

Conclusions

We demonstrated that TF expression revealed severe SEC damage in grafted liver during both acute cellular rejection and chronic rejection.

Keywords

Tissue factor Sinusoidal endothelial cell Living-donor liver transplantation Thrombomodulin Hyaluronic acid