Removal of Bilirubin with a New Adsorbent System: In Vitro Kinetics

Abstract

Background/Aims: Many potentially toxic molecules accumulate in the blood during hepatic dysfunction. In clinical practice, it is very difficult to remove bilirubin, the most widely studied toxin, and particularly the unconjugated form, strongly albumin-bound. The aim of this in vitro study was to assess irreversible bilirubin adsorption as a protein-bound compound marker, using Cytosorb® (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines. Methods: We performed 4 in vitro experiments, dynamic and static, with different albumin-bilirubin solutions. Results: All experiments showed the resin’s ability to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin loss. No sign of bilirubin release from the charged resin was detected (Experiment 4). Conclusion: Cytosorb® seems a promising artificial liver support, thanks to its ability to adsorb bilirubin and its proven ability to modulate the cytokines involved in hepatic dysfunction.

Efficacy of Divinylbenzenic Resin in Removing Indoxyl Sulfate and P-cresol Sulfate in Hemodialysis Patients: Results from an In Vitro Study and an In Vivo Pilot Trial (xuanro4-Nature 3.2)

“…In the literature, Schädler and coworkers [47] showed a limited albumin loss from baseline after the treatments, indicating that the device had no significant impact on these values. Moreover, Gemelli and coworkers [23] specifically studied the behavior of the investigated adsorbent material regarding protein-bound hepatic toxins, such as bilirubin, observing the ability to irreversibly adsorb bilirubin without affecting albumin, which remained stable (changes less than 5%). Apart from these experiences, we are not aware of any other study focused on albumin behavior with the DVB-PVP sorbent or any comparative studies among different extracorporeal techniques.…”

“…In this field, the most promising adsorbent materials are based on divinylbenzene coated with polyvinylpyrrolidone (DVB-PVP) or cellulose with hexadecyl chains for their high hydrophobic nature and biocompatibility, making them appropriate for the direct use in whole blood. These materials have been reported to remove molecules with chemical characteristics similar to PBUTs, such as albumin-bound bilirubin [22,23] or hydrophobic cytokines [24,25], in several clinical settings. These compounds have a hydrophobic characteristic similar to the microbial-derived metabolites, justifying the rationale for the use of DVB-PVP or cellulosic resins for the absorption of either IS and PCS.…”

An unusual complication after endovascular aneurysm repair for giant abdominal aortic aneurysm with aortocaval fistula: High bilirubin levels

“…An in vitro analysis revealed the efficacy of CytoSorb in eliminating bilirubin, with marginal loss of albumin. 21,22 CytoSorb is a promising liver support device, due to its capacity to adsorb bilirubin and its confirmed capability to modulate the cytokines involved in hepatic dysfunction. In patients with multiorgan failure after surgery, the system is a promising therapeutic choice for critically ill and may help in cytokine reduction, improving organ function.…”

Applications of Cytosorb in clinical practice

“…The device breaks the binding between unconjugated bilirubin and albumin, allowing the device to absorb the bilirubin molecule without affecting patients' albumin serum concentrations. The in vitro study from 2018 confirmed bilirubin removal by Cytosorb without affecting the albumin serum concentration during the process, which was a therapeutic issue with some other methods [31]. The case of cardiac surgery patient showed a bilirubin drop from 24.5 mg/dL to 10.8 mg/dL after three days of Cytosorb therapy [32].…”