Ursodeoxycholic acid for primary biliary cirrhosis.
BACKGROUND
Primary biliary cirrhosis is an uncommon autoimmune liver disease with unknown aetiology. Ursodeoxycholic acid (UDCA) has been used for primary biliary cirrhosis, but the effects remain controversial.


OBJECTIVE
To evaluate the benefits and harms of UDCA on patients with primary biliary cirrhosis against placebo or no intervention.


METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE, SCI-EXPANDED, The Chinese Biomedical CD Database, LILACS, and the references of identified studies. The last search was performed in January 2007.


METHODS
Randomised clinical trials evaluating UDCA versus placebo or no intervention in patients with primary biliary cirrhosis.


METHODS
The primary outcomes were mortality and mortality or liver transplantation. Binary outcomes were reported as odds ratio (OR) or relative risk (RR) and continuous outcomes as weighted mean difference, all with 95% confidence intervals (CI). Meta-regression was used to investigate the associations between UDCA effects and quality of the trial, UDCA dose, trial duration, and patient's severity of primary biliary cirrhosis. We also used Bayesian meta-analytic approach to estimate the UDCA effect as sensitivity analysis.


RESULTS
Sixteen randomised clinical trials evaluating UDCA against placebo or no intervention were identified. Data from three trials have been updated. Nearly half of the trials had high risk of bias. The combined results demonstrated no significant effects favouring UDCA on mortality (OR 0.97, 95% CI 0.67 to 1.42) and mortality or liver transplantation (RR 0.92, 95% CI 0.71 to 1.21). The findings were supported by the Bayesian meta-analyses. UDCA did not improve pruritus, fatigue, autoimmune conditions, liver histology, or portal pressure. UDCA seemed to improve biochemical variables, like serum bilirubin, ascites, and jaundice, but the findings were based on few trials with sparse data. The use of UDCA is significantly associated with adverse events, mainly weight gain.


CONCLUSIONS
This systematic review did not demonstrate any benefit of UDCA on mortality and mortality or liver transplantation of patients with primary biliary cirrhosis. The few beneficial effects could not be due to random errors or outcome reporting bias.
Gong
Yan
Y
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen N, Denmark, 2200. ygong@ctu.rh.dk
Huang
Zhi Bi
ZB
Christensen
Erik
E
Gluud
Christian
C
D000284:Administration, Oral; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid