Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature

Abstract

Background: Acute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments.

Aim: To investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality.

Methods: Eligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively.

Results: Of the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection.

Conclusion: BAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation.

Keywords: Acute liver failure; Bioartificial liver; Clinical trial; Meta-analysis; Preclinical experiment.

Figure 1

Flow chart of study selection.

Figure 2

Effect of bioartificial liver support systems on mortality in acute liver failure humans and large animals. The randomized controlled trials for meta-analysis included 2 clinical trials and 6 preclinical experiments with death events (or survival rate) recorded between 90 h to 7d after application of bioartificial liver support systems. M-H: Mantel-Hanszel; BAL: Bioartificial Liver; CI: Confidence interval.