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.
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.
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).