Hodson E M, Barclay P G, Craig J C, Jones C, Kable K, Strippoli G F M, Vimalachandra D, Webster A C
Children's Hospital at Westmead, Centre for Kidney Research, Locked Bag 4001, Westmead, NSW, Australia 2145.
Cochrane Database Syst Rev. 2005 Oct 19(4):CD003774. doi: 10.1002/14651858.CD003774.pub2.
The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection.
To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients.
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction.
Randomised and quasi-randomised controlled trials comparing antiviral medications with placebo or no treatment, trials comparing different antiviral medications and trials comparing different regimens of the same antiviral medications in recipients of any solid organ transplant.
Two reviewers independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted and recipient CMV serostatus at the time of transplantation.
Thirty two trials (3737 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 trials; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 trials; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 trials; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (seven trials; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss. Meta-regression showed no significant difference in the risk of CMV disease or all-cause mortality by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs. In direct comparison trials, ganciclovir was more effective than aciclovir in preventing CMV disease (seven trials; RR 0.37, 95% Cl 0.23 to 0.60). Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir.
AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.
实体器官移植受者感染巨细胞病毒（CMV）的风险，导致人们频繁使用预防措施，旨在预防与CMV感染相关的临床综合征。
确定抗病毒药物预防实体器官移植受者发生CMV疾病和全因死亡的益处和危害。
我们检索了Cochrane对照试验中央注册库、MEDLINE、EMBASE，以及参考文献列表和会议论文摘要，无语言限制。
比较抗病毒药物与安慰剂或不治疗的随机和半随机对照试验、比较不同抗病毒药物的试验，以及比较同一抗病毒药物不同给药方案的试验，研究对象为任何实体器官移植受者。
两名评价员独立评估试验质量并从每个试验中提取数据。采用随机效应模型进行统计分析，结果以二分变量结局的相对风险（RR）及95%置信区间（CI）表示。采用限制最大似然法进行亚组分析和单变量Meta回归，以估计研究间方差。进行多变量Meta回归，以研究在考虑所使用药物、移植器官和移植时受者CMV血清学状态差异后结果是否改变。
共纳入32项试验（3737名参与者）。与安慰剂或不治疗相比，使用阿昔洛韦、更昔洛韦或伐昔洛韦进行预防可显著降低CMV疾病风险（19项试验；RR 0.42，95%CI为0.34至0.52）、CMV感染风险（17项试验；RR 0.61，95%CI为0.48至0.77）和全因死亡风险（17项试验；RR 0.63，95%CI为0.43至0.92），主要是由于CMV疾病导致的死亡率降低（7项试验；RR 0.26，95%CI为0.08至0.78）。预防措施降低了单纯疱疹和带状疱疹疾病、细菌和原生动物感染的风险，但未降低真菌感染、急性排斥或移植物丢失的风险。Meta回归显示，移植器官或CMV血清学状态对CMV疾病风险或全因死亡风险无显著差异；对于CMV阴性器官的CMV阴性受者无法得出结论。在直接比较试验中，更昔洛韦在预防CMV疾病方面比阿昔洛韦更有效（7项试验；RR 0.37，95%CI为0.23至0.60）。缬更昔洛韦和静脉用更昔洛韦与口服更昔洛韦效果相当。
抗病毒药物预防可降低实体器官移植受者的CMV疾病和CMV相关死亡率。应在CMV阳性受者以及CMV阳性器官移植的CMV阴性受者中常规使用。
