In this retrospective case series, 39 patients with acute liver dysfunction (ALD) and corresponding high levels of bilirubin (>10 mg/dl) were given either CytoSorb integrated into high flux dialysis (n. 33), or the advanced organ support system ADVOS (n. 6). The reasons for admission to the Intensive Care Unit in these extremely ill patients treated with CytoSorb were: Acute Respiratory Dysfunction Syndrome (24.2%), septic shock (15.2%), polytrauma (15.2%), liver transplantation (12.1%), ALF (12.1%), lung transplantation (6.1%), cardiogenic shock (6.1%), and other reasons (9.0%). The reasons for admission in patients treated with ADVOS were acute liver failure (50.0%), cardiogenic shock (33.3%), and liver transplantation (16.7%). Laboratory parameters were evaluated before starting therapy (d-1 and d0) and 12–24 h thereafter (d1). The median bilirubin at d-1 was 14.2 and 18.5 mg/dl, at d0 16.9 and 17.7 mg/dl and at d1 13.2 and 15.9 mg/dl, in the CytoSorb and ADVOS groups, respectively, showing a significant increase in total bilirubin in the period prior to CytoSorb treatment. There was a significant bilirubin reduction during CytoSorb treatment (p < 0.001) and during ADVOS treatment (p = 0.028). Significant decreases of AST (92 kDa), ALT (110 kDa), and GGT (64 kDa), observed during CytoSorb treatment might reflect an improvement of liver function, as direct adsorption is unlikely due to molecular size. The authors note that in addition to the lower than expected mortality (92% v 82.2%), there was also a significant reduction in norepinephrine demand with the use of CytoSorb, resulting in hemodynamic stabilization. The significant reduction in SAPS II during CytoSorb is another indicator of an improvement in the patient’s outcome. The authors conclude liver support systems play an important role in the supportive therapy of patients with ALD. While both, ADVOS and CytoSorb, led to a significant and comparable decrease in bilirubin in critically ill patients, the easy use of CytoSorb might be an advantage compared to other procedures. They note that because CytoSorb is able to be easily integrated into high flux dialysis, for example, it may be possible to use in smaller, less resourced hospitals. Open-access publication: https://pubmed.ncbi.nlm.nih.gov/33986443/