Liu Yuan, Zhang Tao, Zhang Xiaoqing, Ye Ling, Gu Haitao, Zhong Lin, Sun Hongcheng, Song Chenlong, Peng Zhihai, Fan Junwei
Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Oncotarget. 2017 Jul 26;8(41):70250-70261. doi: 10.18632/oncotarget.19606. eCollection 2017 Sep 19.
The purpose of the current study was to investigate individualized therapy of tacrolimus (Tac), as well as complications after liver transplantation (LT) with the known genetic determinants and clinical factors.
In this retrospective study, two cohorts (n=170) from the China Liver Transplant Registry (CLTR) database from July 2007 to March 2015 were included.
Both donors' *3 and recipients' *1G had a correlation with Tac pharmacokinetics at four weeks (all <0.05), except recipients' *1G nearly had an association at week 2 (=0.055). The model of donors' *3, recipients' , and total bilirubin (TBL), for the prediction of Tac disposition, was better than donors' *3 only at week 1, 2, and 3 (=0.010, =0.007, and =0.010, respectively), but not apparent at week 4 (=0.297). Besides, when the value was greater than or equal to 0.6685 after considering the false-positive rate R=10%, the patients were considered to have a faster metabolism, according to the mentioned model. Interestingly, we found that if more than or equal to two alleles A were present in the combination of donors' *3 and recipients' *1G genotype, there was a lower Tac C/D ration at week 1, 2, and 3 (<0.001, =0.001, and <0.001), except at week 4 (=0.082), and the probability of new-onset hypertension was lesser (<0.001).
These data provided a potential basis for a comprehensive approach to predicting the Tac dose requirement in individual patients and provided a strategy for the effective prevention, early diagnosis of new-onset hypertension in Chinese LT recipients.
本研究旨在探讨他克莫司（Tac）的个体化治疗以及肝移植（LT）术后已知遗传决定因素和临床因素相关的并发症。
在这项回顾性研究中，纳入了2007年7月至2015年3月来自中国肝移植注册系统（CLTR）数据库的两个队列（n = 170）。
供体的3和受体的1G均与四周时他克莫司的药代动力学相关（均<0.05），受体的1G在第2周时几乎有相关性（=0.055）。供体的3、受体的1G和总胆红素（TBL）模型用于预测他克莫司的处置情况，在第1、2和3周时比仅用供体的3更好（分别为=0.010、=0.007和=0.010），但在第4周时不明显（=0.297）。此外，根据上述模型，当考虑假阳性率R = 10%后值大于或等于0.6685时，患者被认为代谢较快。有趣的是，我们发现如果供体的3和受体的1G基因型组合中存在两个或更多等位基因A，则在第1、2和3周时他克莫司的C/D比值较低（<0.001、=0.001和<0.001），第4周时除外（=0.082），新发高血压的概率较低（<0.001）。
这些数据为全面预测个体患者他克莫司剂量需求提供了潜在依据，并为有效预防、早期诊断中国肝移植受者新发高血压提供了策略。
