Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2019; 25(27): 3634-3648
Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3634
Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature
Yu-Ting He, Ya-Na Qi, Bing-Qi Zhang, Jian-Bo Li, Ji Bao
Yu-Ting He, Bing-Qi Zhang, Ji Bao, Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Ya-Na Qi, Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Jian-Bo Li, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: He YT and Qi YN contributed equally to the work and are co-first authors. He YT and Bao J designed the research; He YT, Qi YN, and Zhang BQ contributed to literature selection and data extraction; He YT, Qi YN, Bao J, and Li JB contributed to analysis and interpretation of the data; He YT and Qi YN drafted the original manuscript; Bao J and Li JB revised the article; All authors have read the final article and approved the publication of the manuscript.
Conflict-of-interest statement: The authors have no conflict of interests to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ji Bao, PhD, Associate Professor, Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. baoji@scu.edu.cn
Telephone: +86-18980606618 Fax: +86-28-85164033
Received: March 20, 2019
Peer-review started: March 20, 2019
First decision: March 27, 2019
Revised: May 3, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 21, 2019
Processing time: 122 Days and 9.5 Hours
ARTICLE HIGHLIGHTS
Research 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 a potential effect to provide temporary support to bridge patients with acute liver failure to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials, but remained verified. 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.

Research motivation

A systematic review and meta-analysis of the existing literature on the use of BAL among humans and large animals with ALF could help bridge the gap between preclinical experiments and clinical trials regarding the effect of BAL for treating acute liver failure.

Research objectives

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

Research 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 the 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 by including only RCT studies was performed to combine the overall effect of BAL on mortality among humans and large animal, respectively.

Research results

Of 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis results suggested that BAL might reduce the mortality of 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. 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.

Research conclusions

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.

Research perspectives

Our study could provide some suggestions for future clinical trials, preclinical experiments, and transformations. First, alternative cells or methods for acquiring high-quality liver cells in vitro must be identified to achieve clinical-scale goals. Second, the effects of the subgroups, patients with PNF or FHF, and patients with different etiologies should be determined and examined in clinical trials in the future. Finally, the advanced BAL, which proved to have a significant benefit on the survival outcome of the large-animal ALF model, should undergo clinical transformation as much as possible.