Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation

Abstract

Aim Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5′‐triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non‐functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. Methods We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17‐knockdown hepatocyte cell line. Results Recipients transplanted with low STX17‐expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17‐expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29–88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59–24.8, p < 0.01) were independent predictive factors for small‐for‐size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17‐knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17‐knockdown hepatocyte cell line. Conclusion STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.

Donor Skeletal Muscle Quality Affects Graft Mortality After Living Donor Liver Transplantation- A Single Center, Retrospective Study

“…However, liver graft quality does not uniformly decline with donor age, and it is important to assess individual changes in donor grafts because there are individual differences in aging (29). In addition, the several qualitative assessment methods previously reported require liver biopsy (30,31), while this IMAC examination is not invasive, and the IMAC can be measured with CT images obtained before surgery, with no additional burden on the donor. In our study, the IMAC was a predictive factor for graft failure, although it was correlated with donor age.…”