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. 2004;2004(2):CD004481.
doi: 10.1002/14651858.CD004481.pub2.

Colchicine for primary biliary cirrhosis

Y Gong  1 , C Gluud
Affiliations

Colchicine for primary biliary cirrhosis

Y Gong et al. Cochrane Database Syst Rev. 2004.

Abstract

Background: Colchicine has been used for patients with primary biliary cirrhosis because of its immunomodulatory and antifibrotic potential. The therapeutical responses to colchicine in randomised clinical trials were inconsistent.

Objectives: To evaluate the beneficial and harmful effects of colchicine in patients with primary biliary cirrhosis.

Search strategy: We identified trials through electronic searches of The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE (September 2003), and manual searches of bibliographies. We contacted authors of trials and pharmaceutical companies.

Selection criteria: Randomised clinical trials comparing colchicine with any kind of control therapy were included irrespective of language, year of publication, and publication status.

Data collection and analysis: The primary outcomes were the number of deaths and the number of death and/or patients who underwent liver transplantation. Dichotomous outcomes were reported as relative risk (RR) with 95% confidence interval (CI). We examined intervention effects by using both a fixed effect model and a random effects model. Heterogeneity was investigated by subgroup analyses and sensitivity analyses.

Main results: Eleven randomised clinical trials involving 716 patients with primary biliary cirrhosis fulfilled the inclusion criteria. No significant differences were detected between colchicine and placebo/no intervention on the number of deaths (RR 1.21, 95% CI 0.71 to 2.06), the number of deaths and/or patients who underwent liver transplantation (RR 1.00, 95% CI 0.67 to 1.49), liver complications, liver biochemical variables, liver histological measurements, and adverse events. Trial methodology was generally low and some trials had high drop-out rate. A best-worst-case-scenario analysis showed no significant effect of colchicine on mortality (RR 0.59, 95%CI 0.30 to 1.15), while a worst-best-case-scenario analysis showed a significant detrimental effect of colchicine on mortality (RR 2.28, 95% CI 1.17 to 4.44). Colchicine significantly decreased the number of patients without improvement of pruritus (RR 0.75, 95% CI 0.65 to 0.87). However, this estimate was based on only 156 patients from three trials. The effect of the combined treatment with ursodeoxycholic acid was not significantly different from that of colchicine alone.

Reviewers' conclusions: We did not find evidence either to support or refute the use of colchicine for patients with primary biliary cirrhosis. As we are not able to exclude a detrimental effect of colchicine, we suggest that it is only used in randomised clinical trials.

PubMed Disclaimer

Conflict of interest statement

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

Figures

1
1
Relative risk of mortality in patients with primary biliary cirrhosis, alcoholic, and non‐alcoholic liver fibrosis and cirrhosis randomised to colchicine versus placebo/no intervention
1.1
1.1. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 1 Number of deaths.
1.2
1.2. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 2 Number of deaths and/or patients who underwent liver transplantation.
1.3
1.3. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 3 Number of patients who underwent liver transplantation.
1.4
1.4. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 4 Number of patients without improvement of pruritus.
1.5
1.5. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 5 Number of patients without improvement of fatigue.
1.6
1.6. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 6 Number of patients developing liver complications.
1.7
1.7. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 7 Appearence of liver complications.
1.8
1.8. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 8 S‐bilirubin (µmol/L).
1.9
1.9. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 9 S‐alkaline phosphatases (ALP)(IU/L).
1.10
1.10. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 10 S‐gamma‐glutamyltransferase (GGT)(IU/L).
1.11
1.11. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 11 S‐aspartate aminotransferase (AST)(IU/L).
1.12
1.12. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 12 S‐alanine aminotransferase (ALT)(IU/L).
1.13
1.13. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 13 S‐albumin (g/dL).
1.14
1.14. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 14 S‐cholesterol (total) (mmol/L).
1.15
1.15. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 15 Plasma immunoglobulin M (g/L).
1.16
1.16. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 16 Prothrombin time (second).
1.17
1.17. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 17 Liver biopsy findings ‐ dichotomous variables.
1.18
1.18. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 18 Liver biopsy findings ‐ histological score.
1.19
1.19. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 19 Number of patients with adverse events.
1.20
1.20. Analysis
Comparison 1 Colchicine versus placebo/no intervention, Outcome 20 Number of patients with serious adverse events.
2.1
2.1. Analysis
Comparison 2 Colchcine ‐ colchicine versus placebo ‐ colchicine (including open label period), Outcome 1 Number of deaths.
2.2
2.2. Analysis
Comparison 2 Colchcine ‐ colchicine versus placebo ‐ colchicine (including open label period), Outcome 2 Number of deaths and/or patients who underwent liver transplantation.
3.1
3.1. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 1 Number of deaths.
3.2
3.2. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 2 Number of deaths and/or patients who underwent liver transplantation.
3.3
3.3. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 3 Number of patients who underwent liver transplantation.
3.4
3.4. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 4 Number of patients without improvement of pruritus.
3.5
3.5. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 5 Number of patients without improvement of fatigue.
3.6
3.6. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 6 Appearance of liver complications.
3.7
3.7. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 7 S‐bilirubin (µmol/L).
3.8
3.8. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 8 S‐alkaline phosphatases (ALP)(IU/L).
3.9
3.9. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 9 S‐gamma‐glutamyltransferase (GGT)(IU/L).
3.10
3.10. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 10 S‐aspartate aminotransferase (AST)(IU/L).
3.11
3.11. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 11 S‐alanine aminotransferase (ALT)(IU/L).
3.12
3.12. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 12 S‐albumin (g/dL).
3.13
3.13. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 13 S‐cholesterol (total) (mmol/L).
3.14
3.14. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 14 Plasma immunoglobulin M (g/L).
3.15
3.15. Analysis
Comparison 3 Colchicine versus ursodeoxycholic acid, Outcome 15 Number of patients with adverse events.
4.1
4.1. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 1 Number of deaths and/or patients who underwent liver transplantation.
4.2
4.2. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 2 Pruritus score.
4.3
4.3. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 3 Fatigue score.
4.4
4.4. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 4 S‐bilirubin (µmol/L) (presented as logtransformed geometric mean).
4.5
4.5. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 5 S‐alkaline phosphatases (ALP)(IU/L) (presented as logtransformed geometric mean).
4.6
4.6. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 6 S‐aspartate aminotransferase (AST)(IU/L) (presented as logtransformed geometric mean).
4.7
4.7. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 7 S‐alanine aminotransferase (ALT)(IU/L) (presented as logtransformed geometric mean).
4.8
4.8. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 8 S‐albumin (g/dL).
4.9
4.9. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 9 S‐cholesterol (total) (mmol/L) (presented as logtransformed geometric mean).
4.10
4.10. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 10 Plasma immunoglobulin M (g/L) (presented as logtransformed geometric mean).
4.11
4.11. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 11 Prothrombin time (second).
4.12
4.12. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 12 Liver biopsy findings ‐ histological stage.
4.13
4.13. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 13 Liver biopsy findings ‐ histological score.
4.14
4.14. Analysis
Comparison 4 Colchicine versus methotrexate, Outcome 14 Number of patients with adverse events.
5.1
5.1. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 1 Number of deaths ‐ dose variation.
5.2
5.2. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 2 Number of deaths ‐ treatment duration.
5.3
5.3. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 3 Number of deaths ‐ generation of the allocation sequence.
5.4
5.4. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 4 Number of deaths ‐ allocation concealment.
5.5
5.5. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 5 Number of deaths ‐ blinding.
5.6
5.6. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 6 Number of deaths and/or patients who underwent liver transplantation ‐ dose variation.
5.7
5.7. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 7 Number of deaths and/or patients who underwent liver transplantation ‐ treatment duration.
5.8
5.8. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 8 Number of deaths and/or patients who underwent liver transplantation ‐ allocation sequence generation.
5.9
5.9. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 9 Number of deaths and/or patients who underwent liver transplantation ‐ allocation concealment.
5.10
5.10. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 10 Number of deaths and/or patients who underwent liver transplantation ‐ blinding.
5.11
5.11. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 11 S‐bilirubin (µmol/L) ‐ reported as arithmetic mean or geometric mean.
5.12
5.12. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 12 S‐cholesterol (total) (mmol/L) ‐ reported as arithmetic mean or geometric mean.
5.13
5.13. Analysis
Comparison 5 Subgroup analyses ‐ colchicine versus placebo/no intervention, Outcome 13 S‐alkaline phosphatase (ALP) (IU/L) ‐ reported as arithmetic mean or geometric mean.
6.1
6.1. Analysis
Comparison 6 Sensitivity analyses ‐ colchicine versus placebo/no intervention, Outcome 1 Number of deaths.
6.2
6.2. Analysis
Comparison 6 Sensitivity analyses ‐ colchicine versus placebo/no intervention, Outcome 2 Number of deaths and/or patients who underwent liver transplantation.
6.3
6.3. Analysis
Comparison 6 Sensitivity analyses ‐ colchicine versus placebo/no intervention, Outcome 3 Number of deaths and/or patients who underwent liver transplantation (excluding Bodenheimer 1988).
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Update of

  • doi: 10.1002/14651858.CD004481

References

References to studies included in this review

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