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Meta-Analysis
. 2004 Oct 18;2004(4):CD004789.
doi: 10.1002/14651858.CD004789.pub2.

D-penicillamine for primary biliary cirrhosis

Y Gong  1 , S L Frederiksen, C Gluud
Affiliations
Meta-Analysis

D-penicillamine for primary biliary cirrhosis

Y Gong et al. Cochrane Database Syst Rev. .

Abstract

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.

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

Search strategy: 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main 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).

Reviewers' 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.

PubMed Disclaimer

Conflict of interest statement

None known. We have no affiliations or financial contracts with companies producing the drugs examined in this review.

Figures

1.1
1.1. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 1 Mortality (expressed as relative risk) ‐ fixed effect model.
1.2
1.2. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 2 Mortality (expressed as relative risk) ‐ random effects model.
1.3
1.3. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 3 Subgroups of methodological quality ‐ generation of allocation sequence ‐ mortality.
1.4
1.4. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 4 Subgroups of methodological quality ‐ allocation concealment ‐ mortality.
1.5
1.5. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 5 Subgroups of methodological quality ‐ blinding ‐ mortality.
1.6
1.6. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 6 Subgroups of methodological quality ‐ follow‐up ‐ mortality.
1.7
1.7. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 7 Subgroups of dosage ‐ mortality.
1.8
1.8. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 8 Subgroups of treatment and follow‐up duration ‐ mortality.
1.9
1.9. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 9 Subgroups of PBC histological stage ‐ mortality.
1.10
1.10. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 10 Sensitivity analyses ‐ mortality.
1.11
1.11. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 11 Mortality or liver transplantation ‐ fixed effect model.
1.12
1.12. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 12 Mortality or liver transplantation ‐ random effects model.
1.13
1.13. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 13 Patients without improvement of pruritus.
1.14
1.14. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 14 Patients without improvement of liver complications.
1.15
1.15. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 15 Liver histology.
1.16
1.16. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 16 Bilirubin (µmol/L).
1.17
1.17. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 17 Alkaline phosphatases (IU/L).
1.18
1.18. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 18 Aspartate aminotransferase (IU/L).
1.19
1.19. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 19 Alanine aminotransferase (IU/L).
1.20
1.20. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 20 Albumin (g/dL).
1.21
1.21. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 21 Adverse event ‐ fixed effect model.
1.22
1.22. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 22 Adverse event ‐ random effects model.
1.23
1.23. Analysis
Comparison 1 D‐penicillamine versus placebo/no intervention, Outcome 23 Adverse event ‐ excluding Taal 1983 trial.
2.1
2.1. Analysis
Comparison 2 High‐dose D‐penicillamine versus low‐dose D‐penicillamine, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 High‐dose D‐penicillamine versus low‐dose D‐penicillamine, Outcome 2 Patients without improvement of liver histological progression.
2.3
2.3. Analysis
Comparison 2 High‐dose D‐penicillamine versus low‐dose D‐penicillamine, Outcome 3 Adverse event.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD004789

References

References to studies included in this review

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