Gong Y, Christensen E, Gluud C
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Rigshospitalet, Dept. 3344, Blegdamsvej 9, Copenhagen, DENMARK, DK-2100.
Cochrane Database Syst Rev. 2007 Jul 18;2007(3):CD005526. doi: 10.1002/14651858.CD005526.pub2.
Cyclosporin A has been used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been heterogeneous.
To assess the beneficial and harmful effects of cyclosporin A for patients with primary biliary cirrhosis.
Relevant randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, The Chinese Biomedical Database, and LILACS, and manual searches of bibliographies to June 2006. We contacted authors of trials and the company producing cyclosporin A.
Randomised clinical trials comparing cyclosporin A with placebo, no intervention, or another drug were included irrespective of blinding, language, year of publication, and publication status.
Our primary outcomes were mortality, and mortality or liver transplantation. Dichotomous outcomes were reported as relative risk (RR) and if appropriate, Peto odds ratio with 95% confidence interval (CI). Continuous outcomes were reported as weighted mean difference (WMD) or standardised mean difference (SMD). We examined intervention effects by random-effects and fixed-effect models.
We identified three trials with 390 patients that compared cyclosporin A versus placebo. Two of them were assessed methodologically adequate with low-bias risk. Cyclosporin A did not significantly reduce mortality risk (RR 0.92, 95% CI 0.59 to 1.45), and mortality or liver transplantation (RR 0.85, 95% CI 0.60 to 1.20). Cyclosporin A significantly improved pruritus (SMD -0.38, 95% CI -0.63 to -0.14), but not fatigue. Cyclosporin A significantly reduced alanine aminotransferase (WMD -41 U/L, 95% CI -63 to -18) and increased serum albumin level (WMD 1.66 g/L, 95% CI 0.26 to 3.05). Significantly more patients experienced adverse events in the cyclosporin A group than in the placebo group, especially renal dysfunction (Peto odds ratio 5.56, 95% CI 2.52 to 12.27) and hypertension (SMD 0.88, 95% CI 0.27 to 1.48).
AUTHORS' CONCLUSIONS: We found no evidence supporting or refuting that cyclosporin A may delay death, death or liver transplantation, or progression of primary biliary cirrhosis. Cyclosporin A caused more adverse events than placebo, like renal dysfunction and hypertension. We do not recommend the use of cyclosporin A outside randomised clinical trials.
环孢素A已用于原发性胆汁性肝硬化患者，但随机临床试验中的治疗反应存在异质性。
评估环孢素A对原发性胆汁性肝硬化患者的有益和有害影响。
通过检索Cochrane肝胆疾病组对照试验注册库、Cochrane图书馆中的Cochrane对照试验中心注册库（CENTRAL）、MEDLINE、EMBASE、科学引文索引扩展版、中国生物医学数据库和LILACS，并人工检索文献目录至2006年6月，确定相关随机临床试验。我们联系了试验作者和生产环孢素A的公司。
纳入比较环孢素A与安慰剂、无干预或另一种药物的随机临床试验，无论是否采用盲法、语言、发表年份和发表状态。
我们的主要结局是死亡率，以及死亡率或肝移植。二分法结局报告为相对风险（RR），并在适当情况下报告Peto比值比及95%置信区间（CI）。连续结局报告为加权均数差（WMD）或标准化均数差（SMD）。我们通过随机效应模型和固定效应模型检验干预效果。
我们确定了3项试验，共390例患者，比较了环孢素A与安慰剂。其中2项在方法学上评估为充分且偏倚风险低。环孢素A未显著降低死亡风险（RR 0.92，95%CI 0.59至1.45），以及死亡率或肝移植风险（RR 0.85，95%CI 0.60至1.20）。环孢素A显著改善了瘙痒（SMD -0.38，95%CI -0.63至-0.14），但未改善疲劳。环孢素A显著降低了丙氨酸转氨酶（WMD -41 U/L，95%CI -63至-18）并提高了血清白蛋白水平（WMD 1.66 g/L，95%CI 0.26至3.05）。环孢素A组发生不良事件的患者明显多于安慰剂组，尤其是肾功能不全（Peto比值比5.56，95%CI 2.52至12.27）和高血压（SMD 0.88，95%CI 0.27至1.48）。
我们没有发现证据支持或反驳环孢素A可能延迟死亡、死亡或肝移植，或原发性胆汁性肝硬化进展。环孢素A比安慰剂导致更多不良事件，如肾功能不全和高血压。我们不建议在随机临床试验之外使用环孢素A。
