Song Jiu-Lin, Gao Wei, Zhong Yan, Yan Lu-Nan, Yang Jia-Yin, Wen Tian-Fu, Li Bo, Wang Wen-Tao, Wu Hong, Xu Ming-Qing, Chen Zhe-Yu, Wei Yong-Gang, Jiang Li, Yang Jian
Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
World J Gastroenterol. 2016 Feb 14;22(6):2133-41. doi: 10.3748/wjg.v22.i6.2133.
To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT).
We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression.
Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy.
A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial.
探讨肝移植（LT）后最低剂量他克莫司（TAC）对新发糖尿病（NODM）的影响。
回顾性分析1999年3月至2014年9月在华西医院肝移植中心的973例肝移植受者的数据。排除不符合条件的受者后，528例采用以TAC为主方案的受者纳入本研究。我们计算并确定了NODM受者糖尿病诊断当年或非NODM受者随访最后一年的TAC平均谷浓度（cTAC）。使用受试者工作特征曲线确定LT后6个月预测NODM的cTAC平均阈值。LT后TAC相关并发症采用χ²检验评估，总体生存率和移植物生存率采用Kaplan-Meier法评估。LT后NODM的危险因素通过单因素和多因素Cox回归分析。
528例移植受者中，131例（24.8%）在LT后6个月发生NODM，NODM的累积发病率逐渐升高。NODM组受者的cTAC平均值显著高于非NODM组受者（7.66±3.41 ng/mL对4.47±2.22 ng/mL，P<0.05）。此外，NODM组受者的1年、5年、10年总体生存率（86.7%、71.3%和61.1%对94.7%、86.1%和83.7%，P<0.05）和移植物生存率（92.8%、84.6%和75.7%对96.1%、91%和86.1%，P<0.05）低于其他组。LT后6个月预测NODM的最佳cTAC平均阈值为5.89 ng/mL。多因素分析显示，LT时年龄较大（>50岁）、LT前高血压以及LT后6个月cTAC平均水平较高（≥5.89 ng/mL）是发生NODM的独立危险因素。同时，cTAC水平较低（<5.89 ng/mL）的受者LT后发生肥胖（21.3%对30.2%，P<0.05）、血脂异常（27.5%对44.8%，P<0.05）、慢性肾功能不全（14.6%对22.7%，P<0.05）和中重度感染（24.7%对33.1%，P<0.05）的可能性低于cTAC平均水平较高组的受者。然而，两组在急性和慢性排斥反应、高血压、心血管事件和新发恶性肿瘤的发生率方面无显著差异。
最低TAC方案可降低LT后长期发生NODM的风险。LT后将cTAC值维持在5.89 ng/mL以下是安全有益的。
