Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Cellular and Molecular Biology, Graduate School of Pharmaceutical Sciences, Hiroshima University, Hiroshima, Japan.
PLoS One. 2019 Mar 7;14(3):e0213462. doi: 10.1371/journal.pone.0213462. eCollection 2019.
It has been reported that donor age affects patient outcomes after liver transplantation, and that telomere length is associated with age. However, to our knowledge, the impact of donor age and donor liver telomere length in liver transplantation has not been well investigated. This study aimed to clarify the influence of the length of telomere and G-tail from donor livers on the outcomes of living donors and recipients after living donor liver transplantation. The length of telomere and G-tail derived from blood samples and liver tissues of 55 living donors, measured using the hybridization protection assay. The length of telomeres from blood samples was inversely correlated with ages, whereas G-tail length from blood samples and telomere and G-tail lengths from liver tissues were not correlated with ages. Age, telomere, and G-tail length from blood did not affect postoperative liver failure and early liver regeneration of donors. On the other hand, the longer the liver telomere, the poorer the liver regeneration tended to be, especially with significant difference in donor who underwent right hemihepatectomy. We found that the survival rate of recipients who received liver graft with longer telomeres was inferior to that of those who received liver graft with shorter ones. An elderly donor, longer liver telomere, and higher Model for End-Stage Liver Disease score were identified as independent risk factors for recipient survival after transplantation. In conclusion, telomere shortening in healthy liver does not correlate with age, whereas longer liver telomeres negatively influence donor liver regeneration and recipient survival after living donor liver transplantation. These results can direct future studies and investigations on telomere shortening in the clinical and experimental transplant setting.
据报道,供体年龄会影响肝移植后患者的预后,端粒长度与年龄有关。然而,据我们所知,供体年龄和供体肝端粒长度对肝移植的影响尚未得到充分研究。本研究旨在阐明供体肝端粒和 G 尾的长度对活体肝移植供体和受者结局的影响。使用杂交保护检测法测量了 55 名活体供体的血液样本和肝组织中端粒和 G 尾的长度。血液样本中端粒的长度与年龄呈负相关,而血液样本中的 G 尾长度以及肝组织中的端粒和 G 尾长度与年龄均无相关性。年龄、血液样本中端粒和 G 尾的长度均不影响供体术后肝功能衰竭和早期肝再生。另一方面,肝端粒越长,肝再生越差,特别是右半肝切除的供体差异显著。我们发现,接受较长端粒肝移植物的受者的存活率低于接受较短端粒肝移植物的受者。老年供体、较长的肝端粒和较高的终末期肝病模型评分被确定为移植后受者存活的独立危险因素。总之,健康肝中端粒缩短与年龄无关,而较长的肝端粒则对活体肝移植后供体肝再生和受者存活产生负面影响。这些结果可以为临床和实验移植环境中端粒缩短的未来研究和调查提供指导。