Abstract Background and Aims In subjects with multiorgan failure and in need for CRRT, new onset of jaundice is associated with a significant mortality. Recent research suggests that elevated serum bile acids contribute to severe immune dysfunction, hepatocellular apoptosis, vasodilation, tubular necrosis and thereby are important drivers of multi-organ failure in new onset of liver dysfunction. Extracorporeal Albumin Detoxification and Dialysis (ECAD) and Hemoperfusion have been used to sustain or recover organ function. Recently, Cytosorb, a hemoperfusion device developed for the removal of proinflammatory molecules in cytokine storm showed a reduction of bilirubin and bile acids in vitro. The aim of this study was to compare the reduction of small albumin bound bile acids with the current standard (ECAD), which was developed not to affect the plasma proteome but effectively remove toxins. Method After obtaining consent, plasma samples were obtained from the extracorporeal circuit of subjects on CRRT due to acute on chronic liver failure (ACLF) and bile acids above 50 µmol/l before and after a day of treatment from the venous and arterial ports and the total removed bile acids were calculated by Area under the curve calculation. The measurements were done during Cytosorb treatments versus during ECAD using a new Albunique Device based on a new recycling technology. Results Despite a high initial reduction rate the capacity of Cytosorb decreased and the total amount of extracorporeal removal was 1720+1189 µmol whereas Albunique removed 7111+2556 µmol, more than 4 times as much and was not saturated after 24 hours. Conclusion Although Cytosorb may prove a role in ACLF with hyperinflammation in the future, hemoperfusion appears to loose efficacy for toxic, albumin bound small molecules and therapies based on diffusion appear to be more cost effective and less additional effects with an unclear impact on the course of ACLF.