Abstract
IntroductionCytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Extracorporeal liver support systems may exert beneficial effects in ACLF via removal of cytokines. At present, two systems are commercially available, the Molecular Adsorbent Recirculating System (MARS™) and Fractionated Plasma Separation, Adsorption and Dialysis (Prometheus™). The aim of this study was to compare the effects of MARS and Prometheus treatments on serum cytokine levels and their clearances.MethodsEight patients with ACLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Thirty-four treatments (17 MARS, 17 Prometheus) were available for analysis. Serum cytokines were measured before and after each treatment, and cytokine clearance was calculated from paired arterial and venous samples and effective plasma flow one hour after the start of treatment.ResultsBaseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and soluble TNF-α receptor 1 were significantly elevated in patients with ACLF. Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus. In MARS treatments, IL-10 was cleared from plasma more efficiently than IL-6. Clearance of IL-10 was higher in Prometheus than in MARS treatments.ConclusionCytokines are cleared from plasma by both MARS and Prometheus, but neither system is able to change serum cytokine levels. This discrepancy is probably due to a high rate of cytokine production in patients with ACLF.
Highlights
Cytokines are believed to play an important role in acute-on-chronic liver failure (ACLF)
Baseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and soluble TNF-α receptor 1 were significantly elevated in patients with ACLF
Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus
Summary
Cytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Two systems are commercially available, the Molecular Adsorbent Recirculating System (MARSTM) and Fractionated Plasma Separation, Adsorption and Dialysis (PrometheusTM). Research has focused on cellfree systems, such as the Molecular Adsorbent Recirculating System (MARSTM; Gambro AB, Stockholm, Sweden) and the Fractionated Plasma Separation, Adsorption and Dialysis system (PrometheusTM; Fresenius Medical Care AG & Co. KGaA, Homburg, Germany), which provide elimination of albumin-. ACLF = acute-on-chronic liver failure; APACHE II = acute physiology and chronic health evaluation II; ELISA = enzyme-linked immunosorbent assay; IL = interleukin; MARS = molecular adsorbent recirculating system; MELD = model for end-stage liver disease; PlCl = plasma clearance; SIRS = systemic inflammatory response syndrome; SOFA = sepsis-related organ failure assessment; sTNF-αR1 = soluble tumor necrosis factor-alpha receptor 1; TNF-α = tumor necrosis factor-alpha. In Prometheus, the patient's plasma, containing the albumin, is separated by a membrane with a molecular weight cutoff of approximately 250 kDa and directly passed over two columns containing different adsorbents. Water-soluble substances are cleared by a high-flux dialyzer directly inserted into the blood circuit [5,8,9,10]
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