Artificial and bioartificial support systems for liver failure

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.

Author(s)

Jian Ping Liu, Lise Lotte Gluud, Bodil Als‐Nielsen, Christian Gluud

Abstract

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.

Author(s)

Jian Ping Liu, Lise Lotte Gluud, Bodil Als‐Nielsen, Christian Gluud

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Patients with acute‐on‐chronic liver failure may benefit from treatment with the more recently developed artificial support systems. The evidence concerning bioartificial support systems and treatment of patients with acute liver failure seemed less conclusive. However, considering the potential limitations of the evidence, liver support system cannot be recommended for routine use.

Implications for research 

Randomised trials on artificial and bioartificial support systems versus standard medical therapy are warranted. The trend of the data justifies larger trials, preferably involving several clinical sites to increase the external validity.

It is of central importance that the therapeutic potential of one support system compared to standard medical therapy becomes sufficiently studied before such systems are introduced as control interventions to more sophisticated support systems. Therfore, hepatologists ought to collaborate in randomised trials allocating patients to one support system plus 'standard medical therapy' versus the same 'standard medical therapy'. 
 
 Such trials should be adequately designed, including centralised randomisation (using stratification for important prognostic factors) as well as blinded outcome assessment. Such trial should adequately describe aetiology of liver failure. Among outcome measures, all pertinent outcomes and adverse events should be carefully registered. Further, such trials should use an independent data monitoring and safety committee having adequate instructions regarding early arrest of the trial. In the reporting of future trials, authors should follow the recommendations of the CONSORT Statement (www.consort‐statement.org).

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