Bile acids for primary sclerosing cholangitis.
BACKGROUND
Bile acids have been used for treating primary sclerosing cholangitis, but their beneficial and harmful effects remain unclear.


OBJECTIVE
To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis.


METHODS
We searched The Cochrane Hepato-Biliary Group's Trials Register, The Cochrane Library, MEDLINE, EMBASE, and The Chinese Biomedical Database generally from inception through to May 2002.


METHODS
Randomised clinical trials comparing any dose or duration of bile acids versus placebo, no intervention, or another intervention were included. Trials were included irrespective of blinding, language, or publication status.


METHODS
Two reviewers extracted the data. The methodological quality of the trials was evaluated with respect to the generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results were reported by intention-to-treat analysis. The outcomes were presented as relative risks (RR) or weighted mean differences (WMD), both with 95% confidence intervals (CI).


RESULTS
We identified six randomised clinical trials, all with low methodological quality. Patients were treated for three months to six years (median two years). Five trials (183 patients) compared ursodeoxycholic acid versus placebo, and one trial (40 patients) compared ursodeoxycholic acid versus no treatment. Ursodeoxycholic acid did not significantly reduce the risk of death (RR 0.86; 95% CI 0.27 to 2.73); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 0.94; 95% CI 0.63 to 1.42); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.43; 95% CI 0.18 to 1.02). Ursodeoxycholic acid significantly improved serum bilirubin (WMD -14.6 micro mol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (WMD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (WMD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (WMD -260 IU/litre; 95% CI -315 to -205), but not albumin (WMD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was well tolerated.


CONCLUSIONS
Ursodeoxycholic acid leads to a significant improvement in liver biochemistry, but there is insufficient evidence to either support or refute its clinical effects in patients with primary sclerosing cholangitis. Large scale, high-quality randomised clinical trials are needed.
Chen
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W
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, H:S Rigshospitalet, Dept. 7102, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. w.chen@ctu.rh.dk
Gluud
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C
D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013657:Taurodeoxycholic Acid / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D013657:Taurodeoxycholic Acid; D014580:Ursodeoxycholic Acid