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Branched-chain amino acids for hepatic encephalopathy

  • Review
  • Intervention

Authors

  • Bodil Als-Nielsen,

    Corresponding author
    1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Copenhagen, Denmark
    • Bodil Als-Nielsen, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Dept. 3344, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. bodil.als@dadlnet.dk.

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  • Ronald L Koretz,

    1. Olive View - UCLA Medical Center, Department of Medicine, Sylmar, USA
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  • Lise Lotte Gluud,

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

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

Background

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.

Objectives

To evaluate the beneficial and harmful effects of BCAA for patients with hepatic encephalopathy.

Search methods

We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue 3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies.

Selection criteria

Randomised trials comparing BCAA with any kind of control therapy for hepatic encephalopathy were included, regardless of blinding, language, or publication status.

Data collection and analysis

Trial inclusion and data extraction were made independently by two reviewers. Our primary outcome was improvement of hepatic encephalopathy. Statistical heterogeneity was tested using random effects and fixed effect models. Binary outcomes are reported as risk ratios (RR) based on a random effects model.

Main results

Eleven randomised trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or isonitrogenous control were included. The median number of patients in each trial was 55 (range 22 to 75). Follow-up after treatment was reported in four trials (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA significantly increased the number of patients improving from hepatic encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that methodological quality had significant impact on the results. We found no evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to 1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to 1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73, three trials).

Authors' conclusions

We did not find convincing evidence that BCAA had a significant beneficial effect on patients with hepatic encephalopathy. The trials performed in this field were small with short follow-up and most had low methodological quality.

摘要

背景

支鏈胺基酸對於肝性腦病變的治療

肝性腦病變可能因為血漿中支鏈胺基酸與芳香胺基酸的比率減少所引起。因此支鏈胺基酸的治療也許對於肝性腦病變病患有助益。

目標

評估支鏈胺基酸對於肝性腦病變的病患有利和有害的效應。

搜尋策略

作者從Cochrane HepatoBiliary Group Controlled Trials Register (2002年9月), (2002年第3期), MEDLINE (1966年至2002年9月)以及EMBASE (1980年至2002年5月), 手工搜尋的書目和雜誌,試驗的作者,以及醫藥公司找出試驗的資料。

選擇標準

不管盲法,語言或發表狀態,涵括比較支鏈胺基酸與任何對照療法對於肝性腦病變的隨機試驗

資料收集與分析

兩位作者獨立地做了試驗的涵括和數據萃取。我們的主要結果是肝性腦病變的改善。 統計上的異質性使用隨機和固定效應模式做測試。二分類的結果根據隨機效應模式以危險比率(RR)表示。

主要結論

共有11個試驗(556位病患)被納入,其比較支鏈胺基酸與碳水化合物、或新黴素(neomycin)/果乳糖(lactulose)、或者isonitrogenous為控制組來加以評估。每個試驗病患人數的中位數是55(範圍22到75)。有4個試驗報告治療後的追蹤(中位數17天 (範圍6到30天))。與對照組相比,在治療結束時支鏈胺基酸顯著增加肝性腦病變改善的病人數量(risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, 9個試驗)。我們沒有找到支鏈胺基酸對存活影響的證據(RR 1.06, 95% CI 0.98 to 1.14, 8個試驗)或者不利的事件(RR 0.97, 95% CI 0.41 to 2.31, 3個試驗)。敏感性分析顯示方法學的品質對結果有顯著的影響。我們發現並沒有證據顯示,支鏈胺基酸對於肝性腦病變在有適當分配順序(RR 1.01, 95% CI 0.84 to 1.23, 3個試驗)、適當分配隱匿(RR 1.09, 95% CI 0.89 to 1.33, 5個試驗)、或者適當雙盲(RR 1.20, 95% CI 0.83 to 1.73, 3個試驗)的試驗有改善的效應。

作者結論

我們沒找到支鏈胺基酸對於肝性腦病變病患顯著有益之令人信服的證據。在這個領域進行的試驗小型而且是短時間的追蹤,並且大多數只有低方法學上的品質。

翻譯人

本摘要由臺中榮民總醫院王建得翻譯。

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

總結

沒有找到支鏈胺基酸對於肝性腦病變病患有益之令人信服的證據。肝性腦病變發生在慢性肝疾病或猛暴型肝衰竭的病人會合併心智狀態的改變,從腦部功能輕微改變的徵象到深度昏迷。支鏈胺基酸治療被認為可以改善這些症狀。當所有的試驗結合起來,支鏈胺基酸似乎在改善肝性腦病變只有些微的效應。然而,這效應在高品質的試驗中沒有看到。因此,這個回顧無法提供令人信服的證據支持支鏈胺基酸使用在肝性腦病變病患。

Plain language summary

No convincing evidence that branched-chain amino acids have a beneficial effect on patients with hepatic encephalopathy was identified

Hepatic encephalopathy occurs in patients with chronic liver disease or fulminant liver failure and is associated with changes in mental state, ranging from minor signs of altered brain function to deep coma. Treatment with branched-chain amino acids has been proposed to ameliorate the symptoms. When all the identified trials were combined, branched-chain amino acids appeared to have a modest effect in improving encephalopathy. However, this effect was not seen when only trials of high quality were included. Thus, this review did not provide convincing evidence to support the use of branched-chain amino acids for patients with hepatic encephalopathy.

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