D-penicillamine for primary biliary cirrhosis.
BACKGROUND
D-penicillamine is used for patients with primary biliary cirrhosis due to its hepatic copper decreasing and immunomodulatory potentials. The results from randomised clinical trials have been inconsistent.


OBJECTIVE
To systematically review the beneficial and harmful effects of D-penicillamine for patients with primary biliary cirrhosis.


METHODS
We identified trials through electronic searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2003), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2003), MEDLINE (January 1966 to September 2003), EMBASE (January 1980 to September 2003), The Chinese Biomedical CD Database (January 1979 to August 2003), and LILACS (1982 to 2003); through manual searches of bibliographies; and by contacting authors of the trials and pharmaceutical companies.


METHODS
We included randomised clinical trials comparing D-penicillamine with placebo/no intervention or other control intervention irrespective of language, year of publication, and publication status.


METHODS
Two reviewers independently assessed the methodological quality of the trials and extracted data, validated by a third reviewer. The primary outcomes were 1) mortality and 2) a combination of those who died or underwent liver transplantation. We analysed dichotomous outcomes as relative risk (RR) with 95% confidence interval (CI) by a fixed effect model and a random effects model. We investigated sources of heterogeneity by subgroup analyses and tested the robustness of our findings by sensitivity analyses.


RESULTS
We included seven trials randomising 706 patients with primary biliary cirrhosis. D-penicillamine compared with placebo/no intervention tended to increase mortality (RR 1.34, 95% CI 1.09 to 1.64, fixed; RR 1.46, 95% CI 0.85 to 2.50, random). However, there was substantial heterogeneity. No significant differences were detected regarding the risks of mortality or liver transplantation, pruritus, liver complications, progression of liver histological stage, or the levels of liver biochemical variables (except alanine aminotransferase). D-penicillamine versus placebo/no intervention significantly increased the risk of adverse events (RR 3.11, 95% CI 2.33 to 4.16, fixed; RR 4.18, 95% CI 1.38 to 12.69, random).


CONCLUSIONS
D-penicillamine did not appear to reduce the risk of mortality, but significantly increased the occurrences of adverse events in patients with primary biliary cirrhosis. We do not support the use of D-penicillamine for patients with primary biliary cirrhosis.
Gong
Y
Y
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Dept. 7102, Blegdamsvej 9, H:S Rigshospitalet, Copenhagen, DK-2100, Denmark. ygong@ctu.rh.dk
Frederiksen
S L
SL
Gluud
C
C
D002614:Chelating Agents / Q000009:adverse effects*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000401:mortality; D010396:Penicillamine / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic
D002614:Chelating Agents; D010396:Penicillamine