J P Liu1, L L Gluud, B Als-Nielsen, C Gluud. 1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK 2100.
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 STRATEGY: Trials were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1985 - 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 reviewers. 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 0.65-1.12) or bridging to liver transplantation (RR 0.87; 95% CI 0.73-1.05), but a significant beneficial effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52-0.86). 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 0.51-0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71-1.29). Two trials comparing artificial support systems showed significant mortality reductions with intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36-0.94) and no significant difference between five versus ten hours of charcoal haemoperfusion (RR 1.03; 95% CI 0.65-1.62). The incidence of adverse events was inconsistently reported. REVIEWER'S 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.
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 STRATEGY: Trials were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1985 - 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 reviewers. 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 0.65-1.12) or bridging to liver transplantation (RR 0.87; 95% CI 0.73-1.05), but a significant beneficial effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52-0.86). 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 0.51-0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71-1.29). Two trials comparing artificial support systems showed significant mortality reductions with intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36-0.94) and no significant difference between five versus ten hours of charcoal haemoperfusion (RR 1.03; 95% CI 0.65-1.62). The incidence of adverse events was inconsistently reported. REVIEWER'S 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.
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