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Ursodeoxycholic acid for primary biliary cirrhosis

  • Review
  • Intervention

Authors


Abstract

Background

Primary biliary cirrhosis is an uncommon autoimmune liver disease with unknown aetiology. Ursodeoxycholic acid (UDCA) has been used for primary biliary cirrhosis, but the effects remain controversial.

Objectives

To evaluate the benefits and harms of UDCA on patients with primary biliary cirrhosis against placebo or no intervention.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE, SCI-EXPANDED, The Chinese Biomedical CD Database, LILACS, and the references of identified studies. The last search was performed in January 2007.

Selection criteria

Randomised clinical trials evaluating UDCA versus placebo or no intervention in patients with primary biliary cirrhosis.

Data collection and analysis

The primary outcomes were mortality and mortality or liver transplantation. Binary outcomes were reported as odds ratio (OR) or relative risk (RR) and continuous outcomes as weighted mean difference, all with 95% confidence intervals (CI). Meta-regression was used to investigate the associations between UDCA effects and quality of the trial, UDCA dose, trial duration, and patient's severity of primary biliary cirrhosis. We also used Bayesian meta-analytic approach to estimate the UDCA effect as sensitivity analysis.

Main results

Sixteen randomised clinical trials evaluating UDCA against placebo or no intervention were identified. Data from three trials have been updated. Nearly half of the trials had high risk of bias. The combined results demonstrated no significant effects favouring UDCA on mortality (OR 0.97, 95% CI 0.67 to 1.42) and mortality or liver transplantation (RR 0.92, 95% CI 0.71 to 1.21). The findings were supported by the Bayesian meta-analyses. UDCA did not improve pruritus, fatigue, autoimmune conditions, liver histology, or portal pressure. UDCA seemed to improve biochemical variables, like serum bilirubin, ascites, and jaundice, but the findings were based on few trials with sparse data. The use of UDCA is significantly associated with adverse events, mainly weight gain.

Authors' conclusions

This systematic review did not demonstrate any benefit of UDCA on mortality and mortality or liver transplantation of patients with primary biliary cirrhosis. The few observed beneficial effects could be due to random errors or outcome reporting bias.

摘要

背景

aursodeoxycholic acid用於治療原發性膽汁性肝硬化

原發性膽汁性肝硬化是一種罕見的自身免疫性肝病,其有效的治療目前很少。一些隨機臨床試驗發現ursodeoxycholic acid對治療原發性膽汁性肝硬化有一定的療效。

目標

評估口服ursodeoxycholic acid對照安慰劑或無干預法治療原發性膽汁性肝硬化的利弊。

搜尋策略

搜尋截至2001年4月的The Cochrane HepatoBiliary Group Controlled Trials Register,Cochrane Library、 MEDLINE、EMBASE、全文搜索。輸入‘ursodeoxycholic acid’、 ‘UDCA’、‘原發性膽汁性肝硬化’、和‘PBC’進行電子搜索。

選擇標準

評估口服任何劑量的ursodeoxycholic acid對照安慰劑或無干預法治療以任意方法診斷出的原發性膽汁性肝硬化病人的隨機臨床試驗。 只包括採用適當隨機化方法的試驗,但不管其盲法及語言。

資料收集與分析

透過組成分析和Jadad 量表評估隨機臨床試驗的品質。摘錄下列結果:死亡率、肝移植、瘙癢、其他臨床症狀 (黃疸、門靜脈壓力 (出血)食道靜脈曲張、腹水、肝性腦病、肝腎症狀、自體免疫條件)、肝臟生化功能、肝臟功能、肝臟切片檢查、生活品質和不良事件。所有分析依據治療意向執行。

主要結論

找出共有16個評估ursodeoxycholic acid對照安慰劑(n = 15) 或無干預法 (n = 1)治療病人的隨機臨床試驗。Jadad量表的中間值是3 (範圍 1 – 5分),許多描述為雙盲法的試驗出現盲法的問題。ursodeoxycholic acid(如果採用劑量8 – 15 mg/kg/day,持續3個月−5年)對死亡(odds ratio = 0.94; 95%CI 0.60 1.48),肝移植 (odds ratio = 0.83; 95% CI 0.52 1.32),死亡或肝移植 (odds ratio = 0.90; 95% CI 0.65 1.26)、瘙癢、疲勞、自身免疫條件、生活品質、肝臟組織學、或門靜脈壓力沒有顯著影響。但是,ursodeoxycholic acid(顯著水平(P < 0.05)降低腹水、黃疸和生化變數,例如血清膽紅素和肝臟酵素。ursodeoxycholic acid和不良事件沒有呈顯著相關。包括後來把病人轉入ursodeoxycholic acid解盲組後,確認ursodeoxycholic acid對於死亡,死亡或肝移植沒有顯著作用。但是,觀察到該藥物對肝移植 (odds ratio = 0.68; 95% CI 0.48 −0.98)的發生率有顯著作用 (P = 0.04) 。

作者結論

ursodeoxycholic acid對原發性膽汁性肝硬化具有邊緣的治療功效。 從積極的一面考慮,ursodeoxycholic acid的副作用很少。 需要對ursodeoxycholic acid治療原發性膽汁性肝硬化的綜合應用進行重新評估。

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

ursodeoxycholic acid可能無法認為可以廣泛地有效治療原發性膽汁性肝硬化。 原發性膽汁性肝硬化是一種罕見的膽汁滯留性肝病,主要發生在中年婦女。原發性膽汁性肝硬化 表現自體免疫的特點,難以找到其有效的治療方案。ursodeoxycholic acid屬於一種膽汁酸 在人體內僅占膽管膽汁的3%。 如果由於膽汁淤積,導致在肝臟中滯留, ursodeoxycholic acid對肝細胞病毒則會少於其他膽汁酸。持續3個月到5年使用ursodeoxycholic acid(8 – 5mg/kg/每天)治療原發性膽汁性肝硬化的病人並未顯著影響死亡率、肝移植、死亡或肝移植、瘙癢、疲勞、自身免疫條件、生活品質、肝臟組織學、或門靜脈壓力。但ursodeoxycholic acid顯著降低腹水、黃疸和肝臟生化性。ursodeoxycholic acid和不良事件的增加沒有關聯。需要對ursodeoxycholic acid治療原發性膽汁性肝硬化的療效重新進行評估。

Plain language summary

Ursodeoxycholic acid is not likely to yield a benefit on survival of patients with primary biliary cirrhosis

Primary biliary cirrhosis is an uncommon and slowly progressive autoimmune disease of the liver that primarily attacks middle-aged women. The cause of the disease is unknown. Over the last 30 years, substantial increases in the prevalence of primary biliary cirrhosis have been observed. Primary biliary cirrhosis is now a frequent cause of liver morbidity, and the patients are significant users of health resources, including liver transplantation.

Ursodeoxycholic acid (UDCA) is the only FDA approved drug to treat primary biliary cirrhosis, but the effects remain controversial. This review evaluates if UDCA has any beneficial role to play in relation to primary biliary cirrhosis patients. It includes 16 randomised clinical trials with a total of 1447 patients. The primary outcome measures were mortality and mortality or liver transplantation. Although UDCA showed a reduction in liver biochemistry, jaundice, and ascites, this review did not demonstrate any benefit of ursodeoxycholic acid on mortality and mortality or liver transplantation.The use of UDCA is associated with weight gain and costs. A number of the trials had risk of bias and the topic seems to have selective reporting of outcomes.

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