肝癌肝移植术后免疫抑制方案的网状荟萃分析  

Efficacy evaluation of immunosuppressive regimen after liver transplantation for hepatocellular carcinoma:a network analysis

作　　者：张琳成 詹启帆 赵禹迪 邵初晓 凌孙彬 徐骁[1,2,6] Zhang Lincheng;Zhan Qifan;Zhao Yudi;Shao Chuxiao;Ling Sunbin;Xu Xiao(Zhejang University School of Medicine,Hangzhou 310058,China;Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province,Hangzhou 310006,China;Fourth Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou 310058,China;Department of Hepatobiliary and Pancreatic Surgery,Lishui People's Hospital,Lishui 323000,China;Department of Hepatobiliary and Pancreatic Surgery,Afiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;NHC Key Laboratory of Combined Multi-organ Transplantation,Hangzhou 310003,China)

机构地区：[1]浙江大学医学院,杭州310058 [2]浙江省肿瘤融合研究与智能医学重点实验室,杭州310006 [3]浙江中医药大学第四临床医学院,杭州310058 [4]丽水市人民医院肝胆胰外科,323000 [5]杭州市第一人民医院肝胆胰外科,310003 [6]卫生部多器官联合移植研究重点实验室,杭州310003

出　　处：《中华移植杂志（电子版）》2023年第6期362-371,共10页Chinese Journal of Transplantation(Electronic Edition)

基　　金：国家自然科学基金(92159202);国家自然科学基金(82273270);国家自然科学基金(32171368);国家科技重大专项(2017ZX10203205)。

摘　　要：目的评价肝细胞癌(以下简称肝癌)肝移植术后不同免疫抑制方案的疗效.方法计算机检索PubMed、Medline、Scopus、EMbase、Cochrane Library和中国知网数据库.检索年限为数据库建库时间至2023年8月31日.主要观察指标为移植术后不同时间总体生存率和无复发生存率.利用Cochrane偏倚风险评估工具5.1.0对纳入的研究进行偏倚风险评价.使用R软件基于贝叶斯随机效应一致性模型进行网状荟萃分析.二分类变量结局指标采用比值比(OR)计算,连续变量结局指标采用均数差(MD)计算,均以效应值及95%可信区间(CI)表示.采用I2统计量评价研究间异质性.采用规模缩减因子判断模型收敛性,并绘制Brooks-Gelman-Rubin诊断图.P<0.05为差异有统计学意义.结果最终纳入27篇,其中随机对照试验8项、前瞻性队列研究1项、回顾性队列研究18项,共11410例肝癌肝移植受者.与CNI组和西罗莫司组相比,依维莫司组受者血管侵犯率更高(OR=0.45,95%CI:0.30~0.71;OR=2.20,95%CI:1.24~3.77).与接受以依维莫司为基础免疫抑制方案的肝移植受者相比,接受CNI受者移植后2年(OR:0.44,95%CI:0.21~0.86)、3年(OR:0.49,95%CI:0.25~0.94)、4年(OR:0.21,95%CI:0.10~0.43)、5年(OR:0.20,95%CI:0.07~0.58)和6年(OR:0.18,95%CI:0.07~0.50)总体生存率更低;与接受以西罗莫司为基础免疫抑制方案受者相比,接受CNI的受者移植后1年(OR:0.41,95%CI:0.24~0.66)、2年(OR:0.54,95%CI:0.33~0.88)、3年(OR:0.66,95%CI:0.44~0.99)、4年(OR:0.42,95%CI:0.28~0.60)、5年(OR:0.59,95%CI:0.38~0.90)、6年(OR:0.51,95%CI:0.28~0.82)、7年(OR:0.49,95%CI:0.27~0.84)总体生存率更低.与接受以西罗莫司为基础免疫抑制方案的肝移植受者相比,接受CNI的受者移植后1年(OR:0.43,95%CI:0.23~0.77)、2年(OR:0.57,95%CI:O.34~0.95)、3年(OR:0.56,95%CI:0.34~0.92)和4年(OR:0.47,95%CI:0.21~0.92)无复发生存率均更低.结论相较于以CNI为基础的免疫抑制方案,术后使用以哺乳动物雷帕霉素靶蛋白抑制�Objective To evaluate the efficacy of different immunosuppressive regimens after liver transplantation for hepatocellular carcinoma.Methods PubMed,Medline,Scopus,EMbase,Cochrane Library and China National Knowledge Infrastructure databases were searched.The search period was from the establishment of the database to August 31,2023.The main observation indexes were overall survival rate and recurrence-free survival rate at different time after liver transplantation.The Cochrane bias risk assessment tool 5.1.0 was used to evaluate the bias risk of the included studies.R software was used for network meta-analysis based on Bayesian random effect consistency model.The outcome indicators of dichotomous variables were calculated by odds ratio(OR),and the outcome indicators of continuous variables were calculated by mean difference(MD),which were expressed by effect value and 95%confidence interval(CI).The I2 statistic was used to evaluate the heterogeneity between studies.The potiential scale reduction factor was used to judge the convergence of the model,and the Brooks-Gelman-Rubin diagnostic diagram was drawn.P<0.05 was considered statistically significant.Results Finally,27 articles were included,including 8 randomized controlled trials,1 prospective cohort study and 18 retrospective cohort studies.A total of 11410 liver transplantation recipients with hepatocellular carcinoma were included.Compared with CNI group and sirolimus group,the rate of vascular invasion in everolimus group was higher(OR=0.45,95%CI:0.30-0.71;OR=2.20,95%CI:1.24-3.77).Compared with liver transplant recipients receiving everolimus-based immunosuppressive regimen,recipients receiving CNI had lower overall survival rates at 2 years(OR:0.44,95%CI:0.21-0.86),3 years(OR:0.49,95%CI:0.25-0.94),4 years(OR:0.21,95%CI:0.10-0.43),5 years(OR:0.20,95%CI:0.07-0.58)and 6 years(OR:0.18,95%CI:0.07-0.50)after transplantation.Compared with liver transplant recipients receiving sirolimus-based immunosuppressive regimen,recipients receiving CNI had lower overall s

关 键 词：肝细胞癌 肝移植 免疫抑制方案 西罗莫司 依维莫司 钙调磷酸酶抑制剂 

分 类 号：R735.7[医药卫生—肿瘤]