Non-bioartificial artificial liver support system in acute liver failure: A comprehensive systematic review and meta-analysis of randomized controlled trials

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-02-01 DOI:10.1016/j.clinre.2025.102527

Ruizhi Shi , Xu Hui , Ting Tong , Junfeng Li , Liting Zhang , Kehu Yang

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引用次数: 0

Abstract

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.

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急性肝衰竭的非生物人工肝支持系统：随机对照试验的综合系统评价和荟萃分析。

背景：急性肝衰竭（Acute liver failure， ALF）是严重威胁患者健康的疾病，死亡率高。非生物人工肝支持系统（Non-Bioartificial Liver Support system， NBALSS）已被用作肝移植的过渡性干预措施，但其疗效尚不确定，它也被用作非肝移植候选者的最后一线治疗。目的：本研究的目的是对随机对照试验（rct）进行系统回顾和荟萃分析，以评估NBALSS治疗急性肝衰竭（ALF）的疗效。主要终点是总生存期（OS），次要终点关注炎症因子水平。方法：对PubMed、EMbase、The Cochrane Library、Web of Science、CBM、万方数据库、VIP数据库、中国知网等数据库进行综合检索。搜索时间从数据库建立到2023年7月。两名独立审稿人筛选文献，提取数据，评估所选研究的偏倚风险，并使用GRADE（推荐、评估、发展和评价等级）对证据的确定性进行评级。随机效应和固定效应荟萃分析用于确定干预措施对ALF的平均效果。采用留一检验进行敏感性分析。此外，根据单一NBALSS治疗或两种NBALSS联合治疗和随访时间进行亚组分析。结果：共纳入12项随机对照试验，共824例患者。NBALSS的使用与总生存率（OS）的显著提高[RR=1.42, 95%CI(1.26, 1.61)，低确定性]和总胆红素（TBIL） [MD=-57.60, 95%CI(-79.60, -35.59)，中等确定性]、丙氨酸转氨酶（ALT） [MD=-48.28, 95%CI(-76.57, -19.98)，低确定性]、肿瘤坏死因子（TNF-α） [MD=-1.49, 95%CI(-2.24, -0.73)，极低确定性]、白细胞介素6 (IL-6) [MD=-178.72, 95%CI(-277.37, -80.06)，极低确定性]的显著降低相关。然而，NBALSS对白细胞介素-2 (IL-2) [MD=1.33, 95%CI(-0.33, 3.00)，极低确定性]、白细胞介素-8 (IL-8) [MD=-44.75, 95%CI(-163.04, 73.55)，极低确定性]和序期器官衰竭评分（SOFA） [MD=-4.06, 95%CI(-8.92, 0.80)，极低确定性]的影响仍不确定。结论：中度至极低确定性证据表明，NBALSS可改善ALF患者的OS、生化指标和细胞因子。然而，证据的确定性受到偏见、不一致和不精确风险的限制。需要高质量和更大规模的试验来更好地确定NBALSS对患者重要结局的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.