Intervention Review

D-penicillamine for primary biliary cirrhosis

  1. Yan Gong1,*,
  2. Sarah Louise Klingenberg2,
  3. Christian Gluud3

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 18 OCT 2004

Assessed as up-to-date: 24 AUG 2004

DOI: 10.1002/14651858.CD004789.pub2

How to Cite

Gong Y, Klingenberg SL, Gluud C. D-penicillamine for primary biliary cirrhosis. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD004789. DOI: 10.1002/14651858.CD004789.pub2.

Author Information

  1. 1

    Copenhagen NV, Denmark

  2. 2

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  3. 3

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Yan Gong, Bispeberg Bakke 26C, 2.th, Copenhagen NV, 2400, Denmark. gong_yan2002@yahoo.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 OCT 2004

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 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.

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).

Authors' 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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

D-penicillamine did not reduce the risk of mortality of patients with primary biliary cirrhosis but increased the occurrences of adverse events

Primary biliary cirrhosis is an uncommon, chronic liver disease of unknown etiology. D-penicillamine, a cupruretic drug, has been tested in randomised clinical trials and is used to treat patients with primary biliary cirrhosis. After combining results from seven trials, D-penicillamine did not appear to improve survival of patients. D-penicillamine was associated with a four-time increase of adverse events. There were no significant differences between D-penicillamine and placebo/no intervention with respect to clinical changes, liver histology, and liver biochemistry.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

D青黴胺(Dpenicillamine)用於原發性膽汁性肝硬化

由於可以降低肝臟的銅堆積和免疫調節,D青黴胺(Dpenicillamine)被用於治療原發性膽汁性肝硬化。但是有關該藥物的隨機臨床試驗卻得到不一致的結論。

目標

系統性的文獻回顧D青黴胺(Dpenicillamine)用於治療原發性膽汁性肝硬化病人的利弊

搜尋策略

透過The Cochrane HepatoBiliary Group Controlled Trials Register(2003年,9月), The Cochrane Central Register of Controlled Trials on The Cochrane Library ((CENTRAL) (2003年第3期),MEDLINE (1966年1月 2003年9月), EMBASE (1980年1月 2003年9月), The Chinese Biomedical CD Database (1979年1月−2003年8月), LILACS (1982年−2003年);手動搜索目錄聯繫試驗作者和製藥公司。

選擇標準

我們包括比較D青黴胺(Dpenicillamine)和安慰劑/無干預法或其他控制干預法的隨機臨床試驗,不受語言,發表年份和發表狀態的限制。

資料收集與分析

兩位回顧者單獨評估試驗的方法學品質,提取資料,由三位回顧者驗證。 初步結果是1)死亡率2)死亡人數和肝移植人數的總和。 我們分析兩分法結果,使用固定結果模式和隨機結果模式,記錄成相對風險度(RR) ,95% 信賴區間 (CI) 。透過亞組分析研究異質性來源,並藉由敏感度分析測試我們發現的穩健性。

主要結論

我們收納7項試驗,隨機挑選706位原發性膽汁性肝硬化病人。 比較安慰劑/無干預法,D青黴胺(Dpenicillamine)增加死亡率 (RR 1.34, 95% CI 1.09 1.64, 固定模式 RR 1.46, 95% CI 0.85  2.50,隨機模式)。但結果具有不存在實質意義的異質性。 在死亡率風險、肝移植、瘙癢、肝臟併發症、肝臟病理階段進展、肝臟生化檢驗值(除丙氨酸轉氨?以外)等方面,沒有發現有任何的顯著差異。比較安慰劑/無干預法,D青黴胺(Dpenicillamine)明顯增加不良事件的風險 (RR 3.11, 95% CI 2.33 4.16, 固定模式 RR 4.18, 95% CI 1.38 12.69, 隨機模式).

作者結論

D青黴胺(Dpenicillamine)不能降低原發性膽汁性肝硬化病人遭受的死亡率風險,但是明顯增加了不良事件的發生。我們不支持原發性膽汁性肝硬化病人使用D青黴胺(Dpenicillamine)。.

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

D青黴胺(Dpenicillamine)不能降低原發性膽汁性肝硬化病人遭受的死亡率風險,但是明顯增加了不良事件的發生。 原發性膽汁性肝硬化是一種罕見的慢性肝病,病原不明。 Dpenicillamine, 作為一種排銅藥物,已在隨機臨床試驗中接受檢驗,用於治療原發性膽汁性肝硬化病人。 結合7次試驗的結果之後, D青黴胺(Dpenicillamine)不能提高病人的存活率。 D青黴胺(Dpenicillamine)與可能造成不良事件呈現四倍增加。在臨床變化,肝臟病理和肝臟生化檢驗值方面,D青黴胺(Dpenicillamine)和安慰劑/無干預法沒有顯著差異。