Maiwall Rakhi, Bajpai Meenu, Singh Akanksha, Agarwal Tanvi, Kumar Guresh, Bharadwaj Ankit, Nautiyal Nidhi, Tevethia Harsh, Jagdish Rakesh Kumar, Vijayaraghavan Rajan, Choudhury Ashok, Mathur Rajendra Prasad, Hidam Ashini, Pati Nirupama Trehan, Sharma Manoj Kumar, Kumar Anupam, Sarin Shiv Kumar
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Clin Gastroenterol Hepatol. 2022 Apr;20(4):e831-e854. doi: 10.1016/j.cgh.2021.01.036. Epub 2021 Jan 29.
High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain.
In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5.
ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE.
In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia.
gov (identifier: NCT02718079).
大容量血浆置换（HVPE）可提高急性肝衰竭（ALF）患者的生存率，但人们仍担心容量超负荷和脑水肿加重。
在一项开放标签随机对照试验中，40例连续的ALF患者按1:1随机分为标准药物治疗（SMT）组或标准容量血浆置换（SVPE）联合SMT组。使用离心式血液成分分离法进行SVPE[每次治疗目标血浆量为1.5至2.0个血浆量]，直至达到预期反应。通过脑部成像评估脑水肿。在意向性分析中分析结果。主要结局是21天无移植生存。在基线和第5天分析细胞因子、损伤相关分子模式（DAMPs）和内毒素水平。
纳入的ALF患者年龄为31.5±12.2岁，60%为男性，78%为病毒感染，83%为超急性，70%伴有全身炎症反应综合征（SIRS）。在第5天，与单独的SMT相比，SVPE[平均治疗次数2.15±1.42，置换血浆量中位数5.049L]导致乳酸清除率更高（p = 0.02），SIRS改善（84%对26%；P = 0.02），氨水平降低[（221.5±96.9）对（439±385.6）μg/dl，P = 0.02]和序贯器官衰竭评估（SOFA）评分降低[9.9（±3.3）对14.6（±4.8）；P = 0.001]。没有与治疗相关的死亡。SVPE与更高的21天无移植生存率相关[75%对45%；P = 0.04，风险比0.30，95%置信区间0.01 - 0.88]。SVPE导致促炎细胞因子水平显著降低，抗炎细胞因子增加，同时内毒素和DAMPs减少。
在伴有脑水肿的ALF患者中，SVPE安全有效，可能通过减少细胞因子风暴和氨来提高生存率。
美国国立医学图书馆临床试验注册库（标识符：NCT02718079）
