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

Abstract

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-α 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.

Cytokine Removal with High Cut-Off Membrane: Review of Literature

“…At the end, 3 case reports [15,16,17], 3 studies on animals [18,19,20], 11 in-vitro/ex-vivo studies [13,21,22,23,24,25,26,27,28,29,30,] and 6 randomized clinical trials/observational studies [14,31,32,33,34,35] fulfilled optimum criteria. The main results deriving from this pool constitute this review.…”

Molecular Adsorbent Recirculating System as a Diagnostic and Therapeutic Modality

“…MARS has been shown to provide both protein- and albumin-bound toxin removal, including ammonium, biliary salts, urea, drug metabolites, and others, and in some cases of acute liver injury can help avoid the need for LT [3,4]. Also, it has been reported that MARS decreases serum concentrations of inflammatory mediators, which are considered to be a critical component of the neuropsychiatric findings associated with hepatic encephalopathy [5–7]. …”

Targeting Albumin Binding Function as a Therapy Goal in Liver Failure: Development of a Novel Adsorbent for Albumin Dialysis

“…The new charcoal adsorbent Hepalbin was scaled up (=Hepalbin‐Cluster 12 ; Albutec GmbH, Rostock, Germany) and tested in a 6 h albumin recirculation model against both standard MARS adsorbents (diaMARS IE250; diaMARS AC250) and empty adsorbents as control ( N = 3). The 6 h treatment was realized as previously described and was modified to neglect effects of hemofilter passage. Removing the hemofilter – acting as a first barrier of toxin transfer – from the two‐compartment model leads to the highest possible toxin load for adsorbents within the models’ limits.…”

“…We found that widening the pore size of a membrane increases the removal of strongly albumin bound toxins (e.g. indirect bilirubin) as well as cytokine removal in albumin dialysis .…”