There is no evidence to support azathioprine for patients with primary biliary cirrhosis

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 patients per million population, and estimates of prevalence range from 19 to 240 patients 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 azathioprine in relation to PBC.

The findings of this review are based on two clinical trials with 293 patients. The drug azathioprine was tested versus placebo or no intervention. The primary findings of the review are that azathioprine has no effect on survival, itching, progression of the disease (cirrhosis development), or quality of life. Patients given azathioprine experienced more adverse events than patients given placebo.

Authors' conclusions: 

There is no evidence to support the use of azathioprine for patients with primary biliary cirrhosis. Researchers who are interested in performing further randomised clinical trials should be aware of the risks of adverse events.

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Background: 

Azathioprine is used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been conflicting.

Objectives: 

To assess the benefits and harms of azathioprine for patients with primary biliary cirrhosis.

Search strategy: 

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 September 2005.

Selection criteria: 

Randomised clinical trials comparing azathioprine versus 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) with 95% confidence interval (CI). Continuous outcomes were reported as weighted mean difference (WMD) or standardised mean difference (SMD). We examined the intervention effects by random-effects and fixed-effect models.

Main results: 

We identified two randomised clinical trials with 293 patients. Only one of the trials was regarded as having low bias risk. Azathioprine did not significantly decrease mortality (RR 0.80, 95% CI 0.49 to 1.31, 2 trials). Azathioprine did not improve pruritus at one-year intervention (RR 0.71, 95% CI 0.28 to 1.84, 1 trial), cirrhosis development, or quality of life. Patients given azathioprine experienced significantly more adverse events than patients given no intervention or placebo (RR 2.44, 95% CI 1.14 to 5.20, 2 trials). The common adverse events were rash, severe diarrhoea, and bone marrow depression.

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