Shi Ruizhi, Hui Xu, Tong Ting, Li Junfeng, Zhang Liting, Yang Kehu
The First Clinical Medical College of Lanzhou University, 730000, Lanzhou, China; Evidence-Based Medicine Center, School of Basic Medical Science, Lanzhou University, 730000, Lanzhou, China.
Evidence-Based Medicine Center, School of Basic Medical Science, Lanzhou University, 730000, Lanzhou, China; Centre for Evidence-Based Social Science/Center for Health Technology Assessment, School of Public Health, Lanzhou University, 730000, Lanzhou, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou University, 730000, Lanzhou, China.
Clin Res Hepatol Gastroenterol. 2025 Feb;49(2):102527. doi: 10.1016/j.clinre.2025.102527. Epub 2025 Jan 10.
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.
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.
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.
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.
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.
急性肝衰竭（ALF）对患者健康构成重大威胁，死亡率很高。虽然非生物人工肝支持系统（NBALSS）已被用作肝移植的过渡性干预措施，但其疗效仍不确定，它也被用作不适合肝移植患者的一线治疗方法。
本研究旨在对随机对照试验（RCT）进行系统评价和荟萃分析，以评估NBALSS治疗急性肝衰竭（ALF）的疗效。主要结局是总生存期（OS），次要结局侧重于炎症因子水平。
我们对多个数据库进行了全面检索，包括PubMed、EMbase、Cochrane图书馆、Web of Science、CBM、万方数据库、维普数据库和中国知网数据库。检索时间跨度从各数据库建库至2023年7月。两名独立评审员筛选文献、提取数据、评估所选研究的偏倚风险，并使用GRADE（推荐分级、评估、制定和评价）对证据的确定性进行评级。采用随机效应和固定效应荟萃分析来确定干预措施对ALF的平均效果。使用留一法检验进行敏感性分析。此外，根据单一NBALSS治疗或两种NBALSS联合治疗以及随访时间进行亚组分析。
共纳入12项涉及824例患者的RCT。使用NBALSS与总生存期（OS）显著改善相关[RR = 1.42，95%CI（1.26，1.61），低确定性]，总胆红素（TBIL）显著降低[MD = -57.60，95%CI（-79.60，-35.59），中等确定性]，丙氨酸氨基转移酶（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]和白细胞介素6（IL-6）[MD = -178.72，95%CI（-277.37，-80.06），极低确定性]。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]和序贯器官衰竭评分（SOFA）[MD = -4.06，95%CI（-8.92，0.80），极低确定性]的影响仍不确定。
证据的确定性为中等至极低表明，NBALSS可能改善ALF患者的OS和生化指标、细胞因子。然而，证据的确定性受到偏倚风险、不一致性和不精确性的限制。需要开展高质量、更大规模的试验，以更好地确定NBALSS对患者重要结局的影响。
