Brown Robert S, Fisher Robert A, Subramanian Ram M, Griesemer Adam, Fernandes Milene, Thatcher William H, Stiede Kathryn, Curtis Michael
Center for Liver Disease, Weill Cornell Medicine, New York, NY.
CTI Clinical Trial and Consulting Services, Covington, KY.
Crit Care Explor. 2025 Jan 13;7(1):e1199. doi: 10.1097/CCE.0000000000001199. eCollection 2025 Jan 1.
To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).
Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023.
Two researchers independently screened citations for eligibility and, of eligible studies, retrieved data related to study characteristics, patients and interventions, outcomes definition, and intervention effects. The Cochrane Risk of Bias 2 tool and Joanna Briggs Institute checklists were used to assess individual study risk of bias. Meta-analysis of mortality at 28-30 days post-support system initiation and frequency of at least one serious adverse event (SAE) generated pooled risk ratios (RRs), based on random (mortality) or fixed (SAE) effects models.
Of 17 trials evaluating NBAL/BAL systems, 11 reported 28-30 days mortality and five reported frequency of at least one SAE. Overall, NBAL/BAL was not statistically associated with mortality at 28-30 days (RR, 0.85; 95% CI, 0.67-1.07; p = 0.169) or frequency of at least one SAE (RR, 1.15; 95% CI, 0.99-1.33; p = 0.059), compared with standard medical treatment. Subgroup results on ALF patients suggest possible benefit for mortality (RR, 0.67; 95% CI, 0.44-1.03; p = 0.069). From six reports of W-ECLP (12 patients), more than half (58%) of severe patients were bridged to transplantation and survived without transmission of porcine retroviruses.
Despite no significant pooled effects of NBAL/BAL devices, the available evidence calls for further research and development of extracorporeal liver support systems, with larger RCTs and optimization of patient selection, perfusion durability, and treatment protocols.
系统评价非生物型（NBAL）或生物型人工肝支持系统（BAL）以及全器官体外肝灌注（W-ECLP）系统在急性肝衰竭（ALF）和慢加急性肝衰竭（ACLF）成人患者中的安全性和有效性。
从PubMed/Embase检索中符合条件的NBAL/BAL研究为针对ALF/ACLF成年患者的随机对照试验（RCT），每组不少于10例患者，报告与生存、不良事件、移植率和肝性脑病相关的结局，且发表于2000年1月至2023年7月的英文文献。另外，我们检索了1990年1月至2023年7月发表的评估W-ECLP在ALF或ACLF成年患者中的研究。
两名研究人员独立筛选文献以确定其是否符合条件，并从符合条件的研究中检索与研究特征、患者和干预措施、结局定义以及干预效果相关的数据。使用Cochrane偏倚风险2工具和乔安娜·布里格斯研究所清单来评估个体研究的偏倚风险。基于随机（死亡率）或固定（至少发生一次严重不良事件（SAE）的频率）效应模型，对支持系统启动后28 - 30天的死亡率和至少发生一次SAE的频率进行荟萃分析，得出合并风险比（RR）。
在评估NBAL/BAL系统的17项试验中，11项报告了28 - 30天的死亡率，5项报告了至少发生一次SAE的频率。总体而言，与标准药物治疗相比，NBAL/BAL在28 - 30天死亡率（RR，0.85；95%CI，0.67 - 1.07；p = 0.169）或至少发生一次SAE的频率（RR，1.15；95%CI，0.99 - 1.33；p = 0.059）方面无统计学关联。ALF患者的亚组结果提示可能对死亡率有获益（RR，0.67；95%CI，0.
