Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses.
OBJECTIVE
Ursodeoxycholic acid (UDCA) is used for primary biliary cirrhosis (PBC), but the beneficial effects remain controversial.


METHODS
We performed an updated systematic review to evaluate the benefits and harms of UDCA in patients with PBC. We included randomized clinical trials evaluating UDCA versus placebo or no intervention in patients with PBC. The primary outcomes, mortality and mortality or liver transplantation, were reported as relative risk (RR) with 95% confidence interval (CI). Meta-regression was used to investigate the associations between UDCA effects and the trial's risk of bias, UDCA dose, duration, and PBC severity at trial entry. We used Bayesian meta-analytic approaches as sensitivity analyses.


RESULTS
Sixteen randomized clinical trials (1,447 patients) evaluating UDCA versus placebo or no intervention were identified. Over half of the trials had high risk of bias. Comparing with placebo or no intervention, UDCA did not significantly affect mortality (RR 0.97, 95% CI 0.67-1.42) and mortality or liver transplantation (RR 0.92, 95% CI 0.71-1.21). The findings were supported by the Bayesian meta-analyses. Meta-regression analyses suggested that UDCA effects seem to be associated with patient's disease severity and trial duration. UDCA did not improve pruritus, fatigue, autoimmune conditions, liver histology, or portal pressure. UDCA seemed to improve biochemical variables, such as serum bilirubin, and ascites and jaundice, but the findings were based on few trials with sparse data. The use of UDCA was significantly associated with adverse events, mainly weight gain.


CONCLUSIONS
This updated systematic review did not demonstrate any benefit of UDCA on mortality and mortality or liver transplantation in patients with PBC.
Gong
Yan
Y
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Department 7102, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Huang
Zhibi
Z
Christensen
Erik
E
Gluud
Christian
C
D001499:Bayes Theorem; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000401:mortality; D016031:Liver Transplantation; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D014580:Ursodeoxycholic Acid / Q000009:adverse effects* / Q000627:therapeutic use*; D015430:Weight Gain
D014580:Ursodeoxycholic Acid