CYP3A5基因多态性指导肝细胞癌肝移植术后他克莫司个体化用药的临床研究

Clinical study on individualized medication of tacrolimus after liver transplantation guided by CYP3A5 gene polymorphism for hepatocellular carcinoma

目的:评价根据CYP3A5基因多态性指导肝细胞癌肝移植术后他克莫司个体化用药的安全性和有效性。方法:分析2018年1月至2019年12月120例因原发性肝细胞癌行同种异体原位肝移植受者的临床资料,根据是否进行供、受体CYP3A5基因检测分为个体化用药组和常规用药组,两组分别根据CYP3A5基因型和既往经验决定他克莫司药物的初始剂量。观察两组受者术后14、21、28d及3、6、9、12个月肝功能恢复正常率,记录两组受者急性排斥反应、肾损伤、感染、神经系统症状、新发高血压、新发糖尿病等并发症的发生率以及总生存率。结果:术后14d和术后21d个体化用药组受者肝功能恢复正常率高于常规用药组受者,差异有统计学意义(P=0.039)。两组受者并发症发生率及1、2年总生存率比较,差异无统计学意义(P>0.05)。结论:根据CYP3A5基因多态性指导肝细胞癌肝移植术后他克莫司的个体化用药是安全的,有利于受者获得长期生存。

Objective:To evaluate the safety and efficacy based on CYP3A5 gene polymorphisms in guiding the individualized tacrolimus therapy after liver transplantation for hepatocellular carcinoma.Methods:Clinical data of 120 patients with primary hepatocellular carcinoma were analyzed who underwent orthotopic liver transplantation from January 2018 to December 2019.According to whether the donor and recipient CYP3A5 gene was detected before operation,they were divided into individualized medication group and conventional medication group.The initial dose of tacrolimus was determined according to CYP3A5 genotype and previous experience in the two groups.The recovery rates of liver function at 14,21,28 days and 3,6,9,12 months after operation were observed.The incidence of acute rejection,acute kidney injury,neurological symptoms,infection,de novo hypertension,de novo diabetes and the overall survival rate were recorded.Results:The differences of recovery rate of liver function between the two groups of recipients at 14 days and 21 days after was statistically significant(all P<0.05).There was no significant difference in the incidence of complications and overall 1-year and 2-year survival rates between the two groups(P>0.05).Conclusion:It is safe to guide individualized tacrolimus after liver transplantation according to CYP3A5 gene polymorphism and beneficial to long-term survival for hepatocellular carcinoma recipients.