Abstract:

Objective To explore the risk factors of cytomegalovirus（CMV）infection after liver transplantation by analyzing the difference of clinical characteristics and the intrapatient variability（IPV）intacrolimus of the recipients after liver transplantation. Methods A retrospective cohort study was conducted inpatients who underwent liver transplantation in the Liver transplantation center of the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019. Among the patients of tacrolimus-based immunosuppressionregiments，290 cases were included according to inclusion and exclusion criteria，and were divided into infection group and control group according to the occurrence for CMV infection. Tacrolimus IPV expressed as the coefficientof variation（CV）was calculated from at least 3 tacrolimus trough levels obtained between months 2 and 6 after liver transplantation，P ＜ 0.05 was considered statistically significant. Results As of December 31 2021，290 liver transplant recipients included in the study，the follow-up ranged from 6 to 83 months. The survival time of recipients in CMV infection group was shorter than that in control group〔（1 707.08±225.96）d vs.（2 214.16±45.03）d，P＜0.05〕.The clinical data of recipients in the CMV infection group and the control group included basic characteristics of donor and recipient，operation-related data，postoperative complications，and the tacrolimus C0 of 2 to 6 months after surgery，there were no significant differences（P ＞ 0.05）. However，the incidence of severe infection and acute rejection in CMV infection group were higher than that in control group（31.58% vs. 4.43%，15.79% vs. 0.74%， P ＜ 0.05）. The influence of some variables on the occurrence of CMV infection after liver transplantation was analyzed by the Cox proportional hazards model analyzed. The results showed that the recipients with high tacrolimus CV had a significantly increased risk of CMV infection after liver transplantation（P ＜ 0.05）. Furthermore，the results showed that CMV-IgM positivity before of liver transplantation，postoperative ICU stay time and tacrolimus CV within 2 to 6 months were an independent risk factors for CMV infection after liver transplantation（all P ＜ 0.05）. Conclusion The preoperative CMV-IgM in liver transplant recipients，the time of ICU stay and the high tacrolimus IPV（CV ≥ 34.36%）within 2 to 6 months after surgery were significantly associated with CMV infection after liver transplantation. CMV infection may lead to an increased incidence of severe infection and acute rejection after livertransplantation. 

Key words:

Livertransplantation, Tacrolimus, Intrapatient variability, Coefficient of variation, Cytomegalovirus

摘要：

目的 分析肝移植受者不同临床特征及他克莫司个体内变异度（intrapatient variability，IPV），探讨肝移植术后受者发生巨细胞病毒（cytomegalovirus，CMV）感染的危险因素。 方法 回顾性分析西安交通大学第一附属医院肝移植于 2015 年 1 月至 2019 年 12 月完成的肝移植病例，纳入 290 例以他克莫司为基础免疫抑制方案的受者，按是否发生 CMV 感染分为感染组和对照组。他克莫司 IPV 量化为变异系数（coefficient of variation，CV），收集受者肝移植术后 2 ～ 6 个月门诊检测的他克莫司 C0 计算 CV，P ＜ 0.05为差异有统计学意义。 结果 截至 2021 年 12 月 31 日，290 例受者随访时间为 6 ～ 83 个月，CMV 感染组受者生存时间短于对照组〔（1 707.08±225.96）d 比（2 214.16±45.03）d，P ＜ 0.05〕。CMV 感染组与对照组供、受者的临床特征及术后 2 ～ 6 个月他克莫司 C0 的差异均无统计学意义（均 P ＞ 0.05）。然而，CMV 感染组重症感染和急性排斥反应的发生率均高于对照组（31.58% 比 4.43%，15.79% 比 0.74%，P ＜ 0.05）。 采用 Cox 比例风险模型分析，高他克莫司 CV 的受者出现 CMV 感染的风险明显升高（P ＜ 0.05）。肝移植受者的术前 CMV-IgM、术后重症监护病房（intensive care unit，ICU）停留时间及术后 2 ～ 6 个月高他克莫司 CV 是 CMV 感染的独立危险因素（均 P ＜ 0.05）。 结论 肝移植受者术前 CMV-IgM、术后 ICU 停留时间及术后 2 ～ 6 个月高他克莫司 IPV（CV ≥ 34.36%）与肝移植术后 CMV 感染有明确相关性，且 CMV 感染组可能导致重症感染和急性排斥反应的发生率增高。

关键词:

肝移植 , 他克莫司 , 个体内变异度 , 变异系数 , 巨细胞病毒