Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

Table 1 Comparison of basic characteristics of artificial liver support systems

System	Detoxification methods	Cost	Complexity	Applicability	Detoxification capacity/range	Impaction OS/TFS	Main characteristics
Continuous renal replacement therapy	Diffusion, convection	Low	Low	Broad (all ICUs, HDUs)	Restricted (water-soluble, low and medium molecular weight substances, mainly ammonia, cytokines)	Few data, no RCTs	Simple, no removal of albumin-bound toxins
High-volume hemofiltration	Convection	Low	Low	Broad (all ICUs, HDUs)	Restricted (water-soluble, low and medium molecular weight substances, mainly ammonia, cytokines), but more effectively than CRRT	Few data, no RCTs	Simple, better removal of low and medium sized molecules and cytokines than low-volume. No significant removal of albumin-bound toxins, loss of albumin, nutrients
High cut-off membranes	Diffusion, convection	Low	Low	Broad (all ICUs, HDUs)	Middle molecules up to 60 kDa, protein-bound uremic toxins, cytokines (IL-8, IL-6, and TNF-α)	Few data, no RCTs	Simple, removal of protein-bound-medium sized uremic toxins cytokines. No removal of other albumin bound toxins, loss of albumin
Direct hemoperfusion (Cytosorb)	Adsorption	Medium to high	Medium	Medium (ICUs, HDUs with experience)	Molecules up to 55 kDa, bilirubin, ammonia, bile acids, IL-6, CRP	Few data, no RCTs	Simple, removal of albumin bound toxins, bilirubin, bile acids, cytokines. Needs more literature
Double plasma molecular absorption system	Plasma separation, adsorption	Medium	Medium	Medium (ICUs, HDUs with experience)	Macromolecules, medium-sized plasma protein bound molecules and toxins, bilirubin, inflammatory molecules	Few data, no RCTs	Simple, removal of albumin bound toxins, bilirubin, bile acids, cytokines; needs more literature
Molecular adsorbent recirculating system	Albumin dialysis-diffusion, adsorption, convection	High	High	Limited (special centers)	Albumin-bound molecules < 50 kDa, water-soluble substances, Cytokines (TNF-α, IL-6, IL-1β, and IL-10)	Not found/not found	With available literature, removal of albumin-bound toxins; complex, expensive, limited access, uses exogenous albumin
Fractionated plasma separation and Adsorption-PROMETHE-US	Plasma separation, albumin dialysis-diffusion, adsorption, convection	High	High	Limited (special centres)	Broad (albumin-bound toxins, water-soluble substances of a wide range of molecular weight, cytokines)	Not found/not found	With available literature, removal of albumin-bound toxin; complex, expensive, limited access
Single-pass albumin dialysis	Albumin dialysis-diffusion, convection	Medium	Low	Broad (all ICUs, HDUs)	Albumin-bound substances (bilirubin, bile acids), small-sized (< 500 Da) water-soluble toxins	Few data, no RCTs	Simple, removal of albumin-bound substances, water soluble toxins; high cost of exogenous albumin, metabolic disarrangements
Coupled plasma filtration adsorption	Plasma separation, adsorption, convection	Medium	Medium	Medium (ICUs, HDUs with experience)	Albumin-bound molecules and toxins (bilirubin, tryptophan, phenols, bile acids), cytokines, water soluble toxins	Few data, no RCTs	Simple, removal of albumin-bound toxins, bilirubin, bile acids, cytokines; needs more literature
Plasma exchange	Separation of plasma substances, replacement with FFP	Medium to high, mainly due to the FFP	Medium	Medium (ICUs, HDUs with experience)	Broad (removal of cytokines, albumin-bound and water-soluble toxins, antibodies, immune complexes, lipoproteins)	Beneficial (RCTs and guidelines)	Effective with available literature from RCTs, replaces plasma proteins, clotting factors; expensive, need, cost and complications of blood products

OS: Overall survival; TFS: Transplant-free survival; ICUs: Intensive care units; HDUs: High dependency units; RCTs: Randomized controlled trials; FFP: Fresh frozen plasma; TNF-α: Tumor necrosis factor-alpha; IL: Interleukin; kDa: Kilodalton; CRP: C-reactive protein.