Non‐Cell‐Based Extracorporeal Artificial Liver Systems: Historic Perspectives, Approaches and Mechanisms, Current Applications, and Challenges.

Background: Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients. For transplant‐ineligible patients the objective becomes liver recovery. Methods: We review seven decades of non‐cell‐based ELSS research in humans. Where possible, we emphasize randomized controlled trials (RCTs). When RCTs are not available, we describe the available human clinical data. Results: There are three broad cell‐free approaches to remove protein‐bound toxins (PBTs) and treat liver failure. The first is a dialysate binder suspension. A material that binds the PBT (the binder) is added to the dialysate. Binders include albumin, charcoal, and polystyrene sulfonate sodium. The unbound fraction of the PBT crosses the dialyzer membrane along a chemical gradient and binds to the binder. The second approach is using grains of sorbent fixed in a plastic housing to remove PBTs. Toxin‐laden blood or plasma flows directly through the column. Toxins are removed by binding to the sorbent. The third approach is exchanging toxin‐laden blood, or fractions of blood, for a healthy donor blood product. Most systems lack widespread acceptance, but plasma exchange (PE) is recommended in many guidelines. The large donor plasma requirement of PE creates demand for systems to complement or replace it. Conclusions: Now that PE has become recommended in some, but not all, jurisdictions, we discuss the importance of reporting precise PE protocols and dose. Our work provides an overview of promising new systems and lessons from old technologies to enable ELSS improvement. [ABSTRACT FROM AUTHOR]