Artificial and bioartificial support systems for liver failure

  • Review
  • Intervention

Authors

  • Jian Ping Liu,

    Corresponding author
    1. Beijing University of Chinese Medicine, Centre for Evidence-Based Chinese Medicine , Beijing, China
    Search for more papers by this author
  • Lise Lotte Gluud,

    1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark
    Search for more papers by this author
  • Bodil Als-Nielsen,

    1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Copenhagen, Denmark
    Search for more papers by this author
  • Christian Gluud

    1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark
    Search for more papers by this author

Abstract

Background

Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery.

Objectives

To evaluate beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure.

Search methods

Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), The Cochrane Library (Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1985 to September 2002), and The Chinese Biomedical Database (September 2002), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies.

Selection criteria

Randomised clinical trials on artificial or bioartificial support systems for acute or acute on-chronic liver failure were included irrespective of blinding, publication status, or language. Non-randomised studies were included in explorative analyses.

Data collection and analysis

Data were extracted independently by three authors. Results were presented as relative risks (RR) with 95% confidence intervals (CI). Sources of heterogeneity were explored through sensitivity analyses and meta-regression. The primary outcome was mortality.

Main results

Twelve trials on artificial or bioartificial support systems versus standard medical therapy (483 patients) and two trials comparing different artificial support systems (105 patients) were included. Most trials had unclear methodological quality. Compared to standard medical therapy, support systems had no significant effect on mortality (RR 0.86; 95% CI 0.65 to 1.12) or bridging to liver transplantation (RR 0.87; 95% CI 0.73 to 1.05), but a significant beneficial effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52 to 0.86). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P = 0.03). In subgroup analyses, artificial support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR 0.67; 95% CI 0.51 to 0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71 to 1.29). Two trials comparing artificial support systems showed significant mortality reductions with intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36 to 0.94) and no significant difference between five versus ten hours of charcoal haemoperfusion (RR 1.03; 95% CI 0.65 to 1.62). The incidence of adverse events was inconsistently reported.

Authors' conclusions

This Review indicates that artificial support systems may reduce mortality in acute-on-chronic liver failure. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure. However, considering the strength of the evidence additional randomised clinical trials are needed before any support system can be recommended for routine use.

摘要

背景

肝衰竭的人工型和生物型支援系統

人工型和生物型肝支援系統可以做為急性肝衰竭或慢性肝衰竭急性惡化的病人接受肝移植或康復的橋樑。

目標

評估人工型和生物人工支援系統對於急性肝衰竭和慢性肝衰竭急性惡化的利弊。

搜尋策略

透過Cochrane HepatoBiliary Group Controlled Trials Register (2002年9月)、Cochrane Library(2002年第3期)、MEDLINE (1966年−2002年9月)、EMBASE (1985 年 2002年9月)以及The Chinese Biomedical Database (2002年9月)、手動檢索參考目錄和期刊、試驗作者和製藥公司。

選擇標準

收納人工或生物人工支援系統用於急性肝衰竭和慢性肝衰竭急性惡化的隨機臨床試驗,不受盲法、發表狀況或語言的限制。非隨機研究納入探索性分析。

資料收集與分析

三位回顧作者獨立提取資料。結果以相對風險度(relative risks,RR),95%信賴區間 (CI)表示。使用敏感性分析和統合迴歸探討異質性來源。主要結果是死亡率。

主要結論

收納12項試驗比較人工或生物人工支援系統和標準藥物療法(483 個病人),以及2項試驗(105個病人)比較不同的人工支援系統。多數試驗的研究方法品質項目評估為不清楚。 比起標準藥物療法,支援系統在死亡率(RR 0.86; 95% CI 0.65 – 1.12)或延續至肝移植方面(RR 0.87; 95% CI 0.73 – 1.05)沒有顯著影響,但對肝性腦病變具有顯著有利的療效 (RR 0.67; 95% CI 0.52 – 0.86)。 統合迴歸分析指出, 支援系統的療效取決於肝衰竭類型 (P = 0.03)。 在分組分析中,人工支援系統降低慢性肝衰竭急性惡化的死亡率33% (RR 0.67; 95% CI 0.51 – 0.90),但沒降低急性肝衰竭的死亡率(RR 0.95; 95% CI 0.71 – 1.29)。2項比較人工支援系統的試驗指出, 間歇性血液過濾比持續性血液過濾能使死亡率顯著降低(RR 0.58; 95% CI 0.36 – 0.94),但是使用5小時和10小時活性炭血液灌流相比,死亡率沒有顯著差異 (RR 1.03; 95% CI 0.65 – 1.62)。不良事件的發生率沒有一致性的呈現。

作者結論

本次文獻回顧指出,人工支援系統可使慢性肝衰竭急性惡化的死亡率顯著降低。 人工和生物人工支援系統不能影響急性肝衰竭的死亡率。但是,考慮到證據強度,要建議任何支援系統用於常規使用之前,需要更多的隨機臨床試驗。

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

人工和生物人工肝支援系統看似有效。不管之前是否已有肝病都有可能發展成為肝衰竭(急性肝衰竭或慢性肝衰竭急性惡化)。兩種狀況都非常嚴重,可能致死。 人工和生物人工支援系統可以做為急性肝衰竭或慢性肝衰竭急性惡化的病人接受肝移植或自然恢復的橋樑。 綜合12項小規模的隨機試驗的證據。大部分的試驗的研究品質評量屬不清楚。 整體來說,支援系統不影響死亡率和支撐到肝移植,但有利於肝性腦病。不良事件的風險尚未確立。欲建議常規使用任何支援系統之前,仍需更多的證據。

Plain language summary

The benefit of artificial and bioartificial liver support systems looks promising

Liver failure may develop without pre-existing liver disease (acute liver failure) or with pre-existing liver disease (acute-on-chronic liver failure). Both disorders are serious and may lead to death. Artificial and bioartificial support systems may 'bridge' patients to liver transplantation or spontaneous recovery. Evidence from twelve small randomised trials were combined. Most trials had unclear methodologic quality. Overall, support systems did not appear to affect mortality or bridging to transplantation, but had a beneficial effect on hepatic encephalopathy. The risk of adverse events could not be established. Further evidence is needed before support systems can be recommended for routine use.

Ancillary