Non-Bioartificial Artificial Liver Support System in Acute Liver Failure: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Acute liver failure (ALF) poses a significant threat to patient health with high mortality rates. While Non-Bioartificial Artificial Liver Support system (NBALSS) has been utilized as a transitional intervention to liver transplant, its efficacy remains uncertain, It is also used as a last-line treatment for patients who are not candidates for liver transplantation.

Objective: The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of NBALSS in treating acute liver failure (ALF). The primary outcome was overall survival (OS), while the secondary outcome focused on inflammatory factor levels.

Methods: We conducted a comprehensive search across various databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, Wanfang Database, VIP database, and CNKI database. The search spanned from the inception of the databases to July 2023. Two independent reviewers screened literature, extracted data, assessed bias risk in the selected studies and used GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) to rate the certainty of evidence. Random and fixed effects meta-analyses were used to determine the average effect of the interventions on ALF. The sensitivity analysis was conducted using the leave-one-out test. Additionally, subgroup analyses were carried out based on a singular NBALSS treatment or combined treatment of two NBALSS and follow-up duration.

Results: Twelve RCTs involving 824 patients were identified. The use of NBALSS was associated with a significantly improved overall survival (OS) [RR=1.42, 95%CI (1.26, 1.61), low certainty] and notable reductions in total bilirubin (TBIL) [MD=-57.60, 95%CI (-79.60, -35.59), moderate certainty], alanine aminotransferase (ALT) [MD=-48.28, 95%CI (-76.57, -19.98), low certainty], tumor necrosis factor (TNF-α) [MD=-1.49, 95%CI (-2.24, -0.73), very low certainty], and interleukin 6 (IL-6) [MD=-178.72, 95%CI (-277.37, -80.06), very low certainty]. However, the effects of NBALSS on interleukin-2 (IL-2) [MD=1.33, 95%CI (-0.33, 3.00), very low certainty], interleukin-8 (IL-8) [MD=-44.75, 95%CI (-163.04, 73.55), very low certainty], and Sequential Organ Failure Score (SOFA) [MD=-4.06, 95%CI (-8.92, 0.80), very low certainty] remained uncertain.

Conclusions: Moderate to very low certainty of evidence indicates that NBALSS may improve OS and biochemical indexes, cytokines in patients with ALF. However, the certainty of evidence is limited by risk of bias, incositency and imprecision. High-quality and larger trials are needed to better determine the effect of NBALSS on patient-important outcomes.