白细胞介素2受体拮抗剂对肝移植后新发糖尿病发病及其转归的影响

Influence of interleukin-2 receptor antagonists on the morbidity and prognosis of new-onset diabetes after liver transplantation

目的探讨白细胞介素2受体拮抗剂（interleukin-2 receptor antagonists, IL-2Ra）在肝移植受者中对移植后新发糖尿病（newly-onset diabetes after transplantation, NODAT）发病及其转归的影响。 方法回顾性调查2001年4月至2016年12月在我院肝外科接受同种异体肝移植术的879例患者的术前及术后临床资料，按照术后是否应用IL-2Ra将其分为IL-2Ra使用组和未使用组；按照NODAT是否发生逆转将其分为暂时性NODAT（Transient-NODAT，T-NODAT）和持续性NODAT（Persistent-NODAT，P-NODAT）；并分析IL-2Ra对NODAT、T-NODAT累计发病率及其发病风险的影响，进一步探讨IL-2Ra对肝移植NDOAT患者远期生存的影响。 结果共入组879例肝移植受者，IL-2Ra使用组（549人）共计177人（32.24%）发生NODAT，其中29.38%（52人）发生逆转；未使用组（330人）共计131人（39.70%）发生NODAT，其中26.72%（35人）发生逆转。校正18项相关混杂因素后分析发现，IL-2Ra使用组的NODAT累计发病率显著低于未使用组（校正后P＝0.028），且IL-2Ra是肝移植NODAT发病的独立保护因素（HR＝0.774, 95%CI 0.616～0.973, P＝0.028）；而使用IL-2Ra与否与肝移植NODAT患者的逆转情况并无显著联系。IL-2Ra使用组NODAT患者的生存情况显著优于未使用组（校正后P＝0.001）。 结论使用IL-2Ra可显著降低肝移植受者发生NODAT的风险，并且显著改善肝移植NODAT患者的远期生存。

Objective To explore the influence of interleukin-2 receptor antagonists （IL-2Ra） on the morbidity and prognosis of new onset diabetes after transplantation（NODAT） in liver transplant recipients. Methods Pre- and post-operative clinical data of 879 nondiabetic patients who underwent a liver transplantation between April 2001 and December 2016 were retrospectively studied. All the enrolled patients were divided into IL-2Ra and non-IL- 2Ra groups according to the use of IL-2Ra. Transient-NODAT（T-NODAT） and Persistent-NODAT（P-NODAT） were defined according to whether NODAT would be existed continuously. The impacts of IL-2Ra on the cumulative incidence as well as the risk of NODAT and T-NODAT were analyzed through comparison between patients who used IL-2Ra or not. And influence of IL-2Ra on the long-term survival of NODAT patients was further analyzed. Results Among 879 patients, 177 （ 32.24% ） from the IL-2Ra group （ n = 549 ） developed NODAT and 29.38% （ n = 52 ） of the NODAT reversed, while 131 （39.70%） from the non-IL-2Ra group （ n = 330 ） developed NODAT and 26.72% （ n = 35 ） of the NODAT reversed. After adjusting for 18 possible confounding factors, the IL-2Ra group had significantly decreased cumulative incidence of NODAT over the non-IL-2Ragroup（adjnstedP=0.028）. COX regression analyses showed that IL-2Ra was a protective factor against NODAT development （ HR O. 774 ; 95% C10. 616-0. 973 ; P = 0. 028 ） , while the use of IL-2Ra and the reverse of NODAT did not significantly related. In addition, long-term survival of the NODAT patients were far better in the IL-2Ra group （ adjusted P = 0. 001 ）. Conclusion IL-2Ra significantly reduces the risk of NODAT in liver transplant recipients and is beneficial to the long-term survival of NODAT patients.