Glucocorticosteroids for primary biliary cirrhosis

  • Review
  • Intervention

Authors


Abstract

Background

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of presumed autoimmune etiology, characterised by the destruction of small intrahepatic bile ducts and the eventual development of cirrhosis and liver failure. Its progression may be influenced by immunosuppression. Glucocorticosteroids are potent immunosuppressive agents, but they are associated with significant adverse effects, including osteoporosis.

Objectives

To systematically evaluate the beneficial and harmful effects of glucocorticosteroids versus placebo or no intervention for patients with primary biliary cirrhosis.

Search methods

The Cochrane Hepato-Biliary Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and the full text of the identified studies were searched until June 2004. The search strategy included terms for primary biliary cirrhosis and glucocorticosteroids (including the names of frequently used preparations). Previous research groups and manufacturers were contacted for additional references. No language restrictions were applied.

Selection criteria

Double-blind, single-blind, or unblinded randomised clinical trials evaluating any preparation of glucocorticosteroids versus placebo or no intervention in patients with primary biliary cirrhosis diagnosed by abnormal liver function tests and either anti-mitochondrial antibodies or histology were included. Additional agents were allowed if they were administered to both groups equally.

Data collection and analysis

The quality of the randomised clinical trials was evaluated by methodology components (generation of allocation sequence; allocation concealment; blinding; follow up). Analyses were performed according to the intention-to-treat method with missing data being accounted for by imputation.

Main results

Only two underpowered trials (reporting 36 and 40 patients) were identified. These differed markedly in their inclusion criteria and treatment protocols. Both stated that they used placebo. However, allocation concealment was unclear. Only one trial reported any patient deaths. No significant improvement in mortality was identified (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.10 to 1.76). Improvements in serum markers of liver inflammation and liver histology were identified. Potentially prognostically linked markers such as bilirubin and albumin were incompletely reported. Bone mineral density (weighted mean difference -2.84%, 95% CI -4.16 to -1.53) and the number of patients with any adverse event (OR 8.99, 95% CI 2.15 to 37.58) were significantly increased in the glucocorticosteroid group.

Authors' conclusions

There is insufficient data to support or reject the use of glucocorticosteroids for patients with primary biliary cirrhosis. It may be appropriate to consider a large prospective randomised clinical trial on this topic.

摘要

背景

以腎上腺糖皮質類固醇治療原發性膽汁性肝硬化

原發性膽汁性肝硬化一種慢性持續性的膽汁滯留性肝病,病理學上屬於自身免疫性疾病,表現為肝內膽管破壞,最終發展成為肝硬化及肝衰竭。 它的病程可能受到免疫抑制的影響。腎上腺糖皮質類固醇雖為強效的免疫抑制劑,但卻也伴隨顯著的不良反應如骨質疏鬆等。

目標

系統性地評估腎上腺糖皮質類固醇對照安慰劑或無干預法,治療原發性膽汁性肝硬化病人的利弊。

搜尋策略

搜尋2004年6月以前的Cochrane HepatoBiliary Controlled Trials Register, The Cochrane Library,、 Cochrane Library、 MEDLINE、EMBASE,全文搜索以找出研究。搜尋策略包括搜索「原發性膽汁性肝硬化」和「腎上腺糖皮質類固醇」等術語 (包括常使用的配方名稱)。 我們聯繫先前的研究團隊和廠商,獲取額外參考文獻。沒有語言限制。

選擇標準

我們選擇雙盲法、單盲法或非盲法隨機臨床試驗,來評估比較所有腎上腺糖皮質類固醇配方對照安慰劑,或無干預法,來治療原發性膽汁性肝硬化其診斷標準為(1)肝功能檢驗異常合併(2)抗粒線體抗體陽性或是組織學檢查。 若還有其他的藥物也同等施用在兩組則可以允許納入選擇標準。

資料收集與分析

採用研究方法成分評估隨機臨床試驗的品質 (分配順序的產生、分組隱匿、盲法、後續追蹤等)。根據治療意向分析資料,並且以插補法(imputation)輸入缺失資料,以完成分析。

主要結論

只找到2個信度不足的試驗(分別記錄36位和40位病人)。這2個試驗明顯在病人納入標準和治療方式上都不相同。2次試驗均使用安慰劑。但是我們不清楚其分組隱匿之情形。只有一個試驗記錄任何病人的死亡。(類固醇之使用)在降低死亡率方面未達統計學的意義 (odds ratio(OR) 0.42, 95% CI 0.10 1.76),但可以改善肝炎指標和肝臟病理學。潛在和肝功能有關的指標,如膽紅素和白蛋白的記錄則不充分。腎上腺糖皮質類固醇組的病人,骨密度降低 (加權平均差−2.84%, 95% CI −4.16 – 1.53)和出現不良反應的病人數 (OR 8.99, 95% CI 2.15 – 37.58)均有顯著增加。

作者結論

沒有足夠的資料支持或反對原發性膽汁性肝硬化的病人使用腎上腺糖皮質類固醇。在此議題上應考慮實施大規模的前瞻性隨機臨床試驗。

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

沒有資料支持或反對原發性膽汁性肝硬化的病人使用腎上腺糖皮質類固醇。原發性膽汁性肝硬化一種慢性持續性的膽汁滯留性肝病,屬於自體免疫疾病。疾病臨床進展或可藉由腎上腺糖皮質類固醇改善。在此議題上我們只找出2個小規模隨機臨床試驗,但是由於樣本數不夠大或追蹤時間不夠長,死亡率的改變無法適當被評估。腎上腺糖皮質類固醇可改善肝炎血清指標以及肝臟病理變化,但是都不具臨床顯著性。腎上腺糖皮質類固醇同時也和一些不良事件相關,包括骨密度減少。進一步的試驗來評估腎上腺糖皮質類固醇的有效性是需要的。

Plain language summary

No evidence to support or refute glucocorticosteroids for patients with primary biliary cirrhosis

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of presumed autoimmune aetiology. The clinical course might be improved by glucocorticosteroids. Only two small randomised clinical trials on this topic were identified. The trials were not large enough in terms of sample size or length of follow up to allow changes in mortality to be adequately evaluated. Glucocorticosteroids were associated with improvement in serum markers of inflammation and liver histology, both of which were of uncertain clinical significance. Glucocorticosteroids were also associated with adverse events, including reduced bone mineral density. Further trials are necessary if the effectiveness of glucocorticosteroids is to be properly evaluated.

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