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11 410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剂为基础的免疫抑制方案的肝癌肝移植受者预后更佳.
Abstract
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 11 410 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 survival rates at 1 year(OR:0.41,95％CI:0.24-0.66),2 years(OR:0.54,95％CI:0.33-0.88),3 years(OR:0.66,95％CI:0.44-0.99),4 years(OR:0.42,95％CI:0.28-0.60),5 years(OR:0.59,95％CI:0.38-0.90),6 years(OR:0.51,95％CI:0.28-0.82),and 7 years(OR:0.49,95％CI:0.27-0.84)after transplantation.Compared with liver transplant recipients receiving sirolimus-based immunosuppressive regimen,recipients receiving CNI had lower recurrence-free survival rates at 1 year(OR:0.43,95％CI:0.23-0.77),2 years(OR:0.57,95％CI:0.34-0.95),3 years(OR:0.56,95％CI:0.34-0.92)and 4 years(OR:0.47,95％CI:0.21-0.92)after transplantation.Conclusions Compared with the CNI-based immunosuppressive regimen,the prognosis of liver transplant recipients with hepatocellular carcinoma using the mammalian target of rapamycin inhibitor-based immunosuppressive regimen after transplantation is better.
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