Reduction of Elevated Cytokine Levels in Acute/Acute-on-Chronic Liver Failure Using Super-Large Pore Albumin Dialysis Treatment: An In Vitro Study

Reduction of Elevated Cytokine Levels in Acute/Acute-on-Chronic Liver Failure Using Super-Large Pore Albumin Dialysis Treatment: An In Vitro Study
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DOI:
10.1111/1744-9987.12146
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发表时间:
2014-08-01
影响因子:
1.9
通讯作者:
Eggert, Martin
Eggert, Martin
中科院分区:
医学4区
文献类型:
--
作者:
Dominik, Adrian;Stange, Jan;Eggert, Martin

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已经使用体外肝脏支持装置(例如,G.分子吸附剂再循环系统; MARS)。然而,使用MARS降低ALF/AocLF中升高的细胞因子仍然不足以有效降低患者的血清细胞因子水平。在基于白蛋白透析的体外肝支持装置中,应考虑使用具有更大孔或更高截留值的新膜,以解决这些问题,因为超大孔膜的引入可以平衡细胞因子的高产生率,并进一步改善体内解毒。使用已建立的体外双室白蛋白透析模型,将三种不同孔径的新型膜与MARS Flux膜进行体外细胞因子清除和解毒质量的比较。使用新型大(Emic 2)至超大孔径膜(S20; HCO Gambro)更有效地去除白蛋白结合的毒素。细胞因子IL-6和肿瘤坏死因子-α的清除率使用超大孔膜显著提高。Emic 2膜主要去除IL-6。体外数据表明,在白蛋白透析中使用较大孔径的膜可有效降低升高的细胞因子水平和肝衰竭毒素。使用大至超大孔膜可能会对患者血清细胞因子水平产生影响。结合增加的解毒,这可能导致ALF/AocLF中更高的存活率。已经确定了用于临床评价的有前景的膜。
The removal of small water soluble toxins and albumin-bound toxins in acute liver failure patients (ALF) or acute-on-chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e. g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut-offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super-large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin-bound toxins were removed more efficiently using novel large (Emic2) to super-large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL-6 and tumor necrosis factor-alpha was drastically improved using super-large pore membranes. The Emic2 membrane predominantly removed IL-6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super-large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.