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Cyclosporin A for primary biliary cirrhosis

  • Review
  • Intervention




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.

Search methods

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.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.



以Cyclosporin A治療原發性膽汁性肝硬化

Cyclosporin A 已被用於原發性膽汁性肝硬化之治療,但其隨機臨床試驗之療效具有異質性。


評估Cyclosporin A 用於原發性膽汁性肝硬化病人的利弊。


透過搜索The Cochrane HepatoBiliary Group Controlled Trials 、Register, Cochrane Library 的Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE、Science Citation Index Expanded、 The Chinese Biomedical Database,LILACS,人工搜索2006年6月以前的書目以尋找相關的隨機臨床試驗。我們聯繫試驗作者和生產Cyclosporin A的廠商。


收納CyclosporinA 對照安慰劑,無干預法或其他藥物的隨機臨床試驗,不受盲法、語言、發表年份、發表狀況限制。


我們的主要結果是死亡率以及死亡率或肝移植。 二分法結果以相對風險度(relative risk,RR),如果合適的話,記錄成Peto odds ratio, 及其95% 信賴區間 (CI)。 我們把連續性結果記錄為加權平均差(weighted mean difference ,WMD)或標準平均差 (standardised mean difference ,SMD)。 我們使用隨機效果和固定效果模型來檢視療效。


我們找到3個試驗比較Cyclosporin A和安慰劑,共有390 位病人。 其中2個試驗經過評估認定其研究方法合宜,偏誤風險低。Cyclosporin A 不能明顯降低死亡率(RR 0.92, 95% CI 0.59 – 1.45),死亡率或肝移植(RR 0.85, 95% CI 0.60 – 1.20)。 CyclosporinA 顯著改善瘙癢(SMD −0.38, 95% CI −0.63 – 0.14),但是無法改善疲勞。Cyclosporin A顯著降低alanine aminotransferase (WMD −41 U/L, 95% CI −63 – 18) ,提高血清白蛋白值 (WMD 1.66 g/L, 95% CI 0.26 – 3.05)。CyclosporinA 組的病人比安慰劑組的病人明顯遭受了更多的不良事件,特別是腎損害 (Peto odds ratio 5.56, 95% CI 2.52 – 12.27)和高血壓 (SMD 0.88, 95% CI 0.27 1.48)。


我們發現沒有證據支持或反對CyclosporinA 能夠延遲死亡、死亡或肝移植,原發性膽汁性肝硬化的進展。Cyclosporin A比安慰劑造成更多的不良事件, 比如腎損害和高血壓。 我們不建議在隨機臨床試驗以外使用CyclosporinA 。


此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


CyclosporinA 對原發性膽汁性肝硬化病人的死亡率,肝移植,疾病進展沒有顯著影響,而且服用CyclosporinA的病人將遭受更多的不良事件。 原發性膽汁性肝硬化 (PBC) 是一種慢性肝病,表現為膽道破壞。 每年估計大約每一百萬人有2 – 24人罹病, 該疾病盛行率在每100萬人中約19 – 240人。主要影響中年婦女。預計病人從「有症狀」到「被診斷」的時間約10年−15年。對於原發性膽汁性肝硬化的病因我們還不清楚,但是疾病動態類似「自體免疫疾病」。 因此人們或許可以期待免疫抑制藥物產生的顯著作用(免疫抑制劑)。 本次文獻回顧評估了所有和原發性膽汁性肝硬化有關的免疫抑制劑Cyclosporin A的臨床資料。共找出了3個試驗,以390位病人為基礎作出結論。以Cyclosporin A對照安慰劑進行檢驗。Cyclosporin A對存活率、病程(肝硬化進展)沒有影響。 接受Cyclosporin A的病人比接受安慰劑的病人會遭受更多的不良事件,特別是腎損害和高血壓。次要結果顯示該藥物可以明顯改善瘙癢 和肝指數。我們不建議在隨機臨床試驗以外的領域使用Cyclosporin A 。

Plain language summary

Cyclosporin A was without significant effects on mortality, liver transplantation, or progression of primary biliary cirrhosis, and patients given cyclosporin A experienced more adverse events

Primary biliary cirrhosis (PBC) is a chronic disease of the liver that is characterised by destruction of bile ducts. Estimates of annual incidence range from 2 to 24 people per million population, and estimates of prevalence range from 19 to 240 people per million population. PBC primarily affects middle-aged women. The forecast for the symptomatic patient after diagnosis is between 10 and 15 years. The cause of PBC is unknown, but the dynamics of the disease resemble the group 'autoimmune disease'. Therefore, one might expect a noticeable effect of administering an immune repressing drug (immunosuppressant). This review evaluates all clinical data on the immunosuppressant cyclosporin A for PBC.

The findings in this review are based on three clinical trials with 390 patients. The drug cyclosporin A was tested against placebo. The primary findings of the review are that cyclosporin A has no effect on survival or progression of the disease (cirrhosis development). Patients given cyclosporin A experienced more adverse events than patients given placebo, especially renal dysfunction and hypertension. There was significant improvement in itching (pruritus) and liver biochemistry, which were secondary outcome measures.

We cannot recommend the use of cyclosporin A outside randomised clinical trials.

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