MARS: Should I Use It?

Severe liver failure, including acute liver failure and acute-on-chronic liver failure, is associated with high mortality, and many patients die despite aggressive medical therapy. While liver transplantation is a viable treatment option for liver failure patients, a large proportion of these patients die given the shortage in the liver donation and the severity of illness, leading to death while waiting for a liver transplant. Extracorporeal liver support devices, including molecular adsorbent recirculating system (MARS), have been developed as bridge to transplantation (bridge for patients who are decompensating while waiting for liver transplantation) and bridge to recovery (for whom recovery is deemed reasonable). In addition to its uses in acute liver failure and acute-on-chronic liver failure, the MARS system has also been applied in various clinical settings, such as drug overdosing and poisoning and intractable cholestatic pruritus refractory to pharmacological treatment. This review aims to discuss the controversies, potential benefits, practicalities, and disadvantages of using MARS in clinical practice. Severe liver failure, including acute liver failure and acute-on-chronic liver failure, is associated with high mortality, and many patients die despite aggressive medical therapy. While liver transplantation is a viable treatment option for liver failure patients, a large proportion of these patients die given the shortage in the liver donation and the severity of illness, leading to death while waiting for a liver transplant. Extracorporeal liver support devices, including molecular adsorbent recirculating system (MARS), have been developed as bridge to transplantation (bridge for patients who are decompensating while waiting for liver transplantation) and bridge to recovery (for whom recovery is deemed reasonable). In addition to its uses in acute liver failure and acute-on-chronic liver failure, the MARS system has also been applied in various clinical settings, such as drug overdosing and poisoning and intractable cholestatic pruritus refractory to pharmacological treatment. This review aims to discuss the controversies, potential benefits, practicalities, and disadvantages of using MARS in clinical practice. Clinical Summary•Severe liver failure, including acute liver failure (ALF) and acute on chronic liver failure (AoCLF), is associated with high mortality, and many patients die despite aggressive medical therapy.•Extracorporeal liver support (ECLS) devices, including molecular adsorbent recirculating system (MARS), have been developed as bridge-to-transplantation or bridge-to-recovery.•MARS system has been applied in ALF and AoCLF, drug overdosing and poisoning and intractable cholestatic pruritus refractory to pharmacological treatment.•Future studies are needed to standardize indications, time of initiation, frequency, and duration of the treatments. •Severe liver failure, including acute liver failure (ALF) and acute on chronic liver failure (AoCLF), is associated with high mortality, and many patients die despite aggressive medical therapy.•Extracorporeal liver support (ECLS) devices, including molecular adsorbent recirculating system (MARS), have been developed as bridge-to-transplantation or bridge-to-recovery.•MARS system has been applied in ALF and AoCLF, drug overdosing and poisoning and intractable cholestatic pruritus refractory to pharmacological treatment.•Future studies are needed to standardize indications, time of initiation, frequency, and duration of the treatments. The liver is a complex organ performing vital functions, including detoxification, synthesis, and regulation. Liver diseases lead to more than a million deaths worldwide, and the trend has been markedly rising in the past decade. Death from severe liver failure can occur in the clinical context of acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF). Currently, the overall management of patients with liver failure includes treating the precipitating event and supportive therapy for extrahepatic end-organ dysfunction while hoping for liver recovery or waiting for a liver transplant. Orthotopic liver transplantation is the standard of care for treating irreversible liver failure; however, it is hampered by a growing shortage of donor organ pool. In some clinical scenarios, by the time an organ becomes available, multiorgan dysfunction may have worsened to a severe degree that seriously compromise the post-transplant outcome making patients unsuitable for transplantation. Overall, the mortality rate with medical management varies between 50 and 90%.1Wauters J. Wilmer A. Albumin dialysis: current practice and future options.Liver Int. 2011; 31: 9-12Crossref PubMed Scopus (13) Google Scholar Given the organ shortage for transplantation, efforts are being made to find therapeutic alternatives such as artificial extracorporeal liver support (ECLS) devices as bridge to transplantation (bridge for patients who are decompensating while waiting for liver transplantation) and bridge to recovery (for whom recovery is deemed reasonable ).2Zheng Z. Li X. Li Z. Ma X. Artificial and bioartificial liver support systems for acute and acute-on-chronic hepatic failure: a meta-analysis and meta-regression.Exp Ther Med. 2013; 6: 929-936Crossref PubMed Scopus (45) Google Scholar,3García Martínez J.J. Bendjelid K. Artificial liver support systems: what is new over the last decade?.Ann Intensive Care. 2018; 8: 109Crossref PubMed Scopus (25) Google Scholar Liver failure results in the accumulation of toxins that contribute to multiorgan dysfunction, making the elimination of these toxins a reasonable treatment goal. In human blood, depending on their physicochemical characteristics, toxins from liver failure can be divided into two major groups, 1) water-soluble (e.g., ammonia) or 2) mainly albumin-bound (e.g., bilirubin).4Krisper P. Stauber R.E. Technology insight: artificial extracorporeal liver support--how does Prometheus compare with MARS?.Nat Clin Pract Nephrol. 2007; 3: 267-276Crossref PubMed Scopus (69) Google Scholar Plasma exchange, by which virtually all noncellular blood constituents can be removed, has the potential to eliminate all relevant toxic substances nonspecifically. Conventional dialysis techniques (hemodialysis and hemofiltration) are capable of removing only water-soluble particles. Since the 1990s, multiple ECLS devices, both bioartificial and artificial (albumin dialysis based), have been developed. Bioartificial devices hosting hepatocyte cells (human vs porcine) were promising but far from routine administration due to intrinsic issues related to any bioartificial system.5Demetriou A.A. Brown Jr., R.S. Busuttil R.W. et al.Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.Ann Surg. 2004; 239 (discussion 667-670): 660-667Crossref PubMed Scopus (491) Google Scholar The best-known artificial ECLS devices are 1) the molecular adsorbent recirculating system (MARS; Baxter, Deerfield, Illinois), 2) total plasma exchange (TPE) in combination with conventional hemodialysis, 3) the single-pass albumin dialysis system (SPAD), and 4) fractionated plasma separation and adsorption system (Prometheus; Fresenius Medical Care, Bad Homburg, Germany, 1999).6Kribben A. Gerken G. Haag S. et al.Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.Gastroenterology. 2012; 142: 782-789.e783Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar, 7Kortgen A. Rauchfuss F. Götz M. Settmacher U. Bauer M. Sponholz C. Albumin dialysis in liver failure: comparison of molecular adsorbent recirculating system and single pass albumin dialysis--a retrospective analysis.Ther Apher Dial. 2009; 13: 419-425Crossref PubMed Scopus (35) Google Scholar, 8Ringe H. Varnholt V. Zimmering M. et al.Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure.Pediatr Crit Care Med. 2011; 12: 257-264Crossref PubMed Scopus (0) Google Scholar, 9Karvellas C.J. Bagshaw S.M. McDermid R.C. Stollery D.E. Bain V.G. Gibney R.T. A case-control study of single-pass albumin dialysis for acetaminophen-induced acute liver failure.Blood Purif. 2009; 28: 151-158Crossref PubMed Scopus (0) Google Scholar, 10Liu J.P. Gluud L.L. Als-Nielsen B. Gluud C. Artificial and bioartificial support systems for liver failure.Cochrane Database Syst Rev. 2004; 2004: CD003628Google Scholar, 11Stadlbauer V. Krisper P. Beuers U. et al.Removal of bile acids by two different extracorporeal liver support systems in acute-on-chronic liver failure.Asaio J. 2007; 53: 187-193Crossref PubMed Scopus (40) Google Scholar, 12Krisper P. Haditsch B. Stauber R. et al.In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation.J Hepatol. 2005; 43: 451-457Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar These systems are based on albumin dialysis and possess the ability to eliminate both albumin-bound and water-soluble toxins that occur in patients with liver failure.13Drolz A. Saxa R. Scherzer T. Fuhrmann V. Extracorporeal artificial liver support in hypoxic liver injury.Liver Int. 2011; 31: 19-23Crossref PubMed Scopus (9) Google Scholar, 14Tsipotis E. Shuja A. Jaber B.L. Albumin dialysis for liver failure: a systematic review.Adv Chronic Kidney Dis. 2015; 22: 382-390Abstract Full Text Full Text PDF PubMed Google Scholar, 15Krisper P. Stadlbauer V. Stauber R.E. Clearing of toxic substances: are there differences between the available liver support devices?.Liver Int. 2011; 31: 5-8Crossref PubMed Google Scholar Although SPAD is well-tolerated, it is not shown to be associated with improved survival in patients with liver failure, or referral to liver transplantation in patients with ALF.9Karvellas C.J. Bagshaw S.M. McDermid R.C. Stollery D.E. Bain V.G. Gibney R.T. A case-control study of single-pass albumin dialysis for acetaminophen-induced acute liver failure.Blood Purif. 2009; 28: 151-158Crossref PubMed Scopus (0) Google Scholar Besides, SPAD requires an enormous amount of human serum albumin, which impacts its cost. While data suggest that Prometheus can be used safely in patients awaiting liver transplantation,16Nyckowski P. Skwarek A. Zieniewicz K. et al.Orthotopic liver transplantation for fulminant hepatic failure.Transpl Proc. 2006; 38: 219-220Crossref PubMed Scopus (0) Google Scholar severe coagulation disturbances have been reported.17Meijers B.K. Verhamme P. Nevens F. et al.Major coagulation disturbances during fractionated plasma separation and adsorption.Am J Transpl. 2007; 7: 2195-2199Crossref PubMed Scopus (46) Google Scholar In liver failure, TPE has been shown to reduce serum bilirubin and ammonia and increase coagulation factors leading to improved coagulopathy.18Lee K.C. Stadlbauer V. Jalan R. Extracorporeal liver support devices for listed patients.Liver Transpl. 2016; 22: 839-848Crossref PubMed Google Scholar,19Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar However, TPE does not correct electrolyte disturbances and can result in hypocalcemia and alkalosis.18Lee K.C. Stadlbauer V. Jalan R. Extracorporeal liver support devices for listed patients.Liver Transpl. 2016; 22: 839-848Crossref PubMed Google Scholar To date, MARS has been the most studied and is the most widely used extracorporeal liver support systems.20Zoica B.S. Deep A. Extracorporeal renal and liver support in pediatric acute liver failure [published online ahead of print June 5, 2020].Pediatr Nephrol. 2020; https://doi.org/10.1007/s00467-020-04613-4Crossref PubMed Scopus (0) Google Scholar Nephrologists commonly encounter patients with liver failure and are occasionally involved with MARS therapy. Thus, nephrologists need to be familiar with this novel therapy for a challenging clinical disease. This review aims to discuss the practicalities and controversies surrounding the use of MARS in clinical practice. Stange and Mitzner developed MARS in the 1990s.21Stange J. Ramlow W. Mitzner S. Schmidt R. Klinkmann H. Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins.Artif Organs. 1993; 17: 809-813Crossref PubMed Scopus (185) Google Scholar The system can effectively remove albumin-bound as well as water-soluble substances.1Wauters J. Wilmer A. Albumin dialysis: current practice and future options.Liver Int. 2011; 31: 9-12Crossref PubMed Scopus (13) Google Scholar,3García Martínez J.J. Bendjelid K. Artificial liver support systems: what is new over the last decade?.Ann Intensive Care. 2018; 8: 109Crossref PubMed Scopus (25) Google Scholar,22Struecker B. Raschzok N. Sauer I.M. Liver support strategies: cutting-edge technologies.Nat Rev Gastroenterol Hepatol. 2014; 11: 166-176Crossref PubMed Scopus (115) Google Scholar MARS is used via an additional circuit connected to a standard extracorporeal circuit (continuous kidney replacement circuit), which uses 20% albumin as a dialysis medium. MARS (Figure 1) uses 50-kDa molecular cutoff high-flux polysulfone dialyzer and a secondary circuit, incorporating albumin-enriched dialysate (20% albumin) crossing the filter in a counter directional flow.23Larsen F.S. Artificial liver support in acute and acute-on-chronic liver failure.Curr Opin Crit Care. 2019; 25: 187-191Crossref PubMed Scopus (12) Google Scholar Owing to 50-kDa molecular cutoff, proteins such as immunoglobulins, albumin, and coagulation factors are not removed during therapy. This system enables albumin-bound toxins, but not albumin itself, to dissociate, passing through the membrane to attach to albumin in the secondary circuit. The exogenous albumin dialysate is subsequently regenerated in a closed loop by adsorption through the charcoal and anion-exchange resin columns and by dialysis against a conventional bicarbonate-buffered dialysate. MARS has 2 filters available based on weight. For those >25 kg, the adult filter (2.1 m2, fill volume 152 mL) is appropriate and for those <25 kg, the MARS minifilter (0.6 m2, fill volume 57 mL) is suited, allowing this device to be applied in pediatrics. MARS dialysis can be performed once daily for 8 to 10 hours until adsorber systems are saturated, and continuously for many days, provided the system is exchanged regularly. Both protein-bound and water-soluble toxins have been implicated in pathogenesis and progression to multiorgan dysfunction in severe liver failure.24Mitzner S.R. Stange J. Klammt S. et al.Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.Liver Transpl. 2000; 6: 277-286Crossref PubMed Scopus (584) Google Scholar, 25Mullen K.D. Treatment of hepatorenal syndrome: lessons from the MARS trial.Hepatology. 2002; 35: 492-493Crossref PubMed Scopus (0) Google Scholar, 26Best L.M. Freeman S.C. Sutton A.J. et al.Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis.Cochrane Database Syst Rev. 2019; 9: CD013103PubMed Google Scholar, 27Jain V. Dhawan A. Extracorporeal liver support systems in paediatric liver failure.J Pediatr Gastroenterol Nutr. 2017; 64: 855-863Crossref PubMed Scopus (1) Google Scholar Factors involved in the etiology of hepatic encephalopathy have always been debated. Among the different water-soluble and water-insoluble toxins implicated (i.e., bile acids, aromatic amino acids, cytokines, chemokines, medium-chain fatty acids), ammonia claims an essential role.20Zoica B.S. Deep A. Extracorporeal renal and liver support in pediatric acute liver failure [published online ahead of print June 5, 2020].Pediatr Nephrol. 2020; https://doi.org/10.1007/s00467-020-04613-4Crossref PubMed Scopus (0) Google Scholar,28Bañares R. Ibáñez-Samaniego L. Torner J.M. et al.Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity.Therap Adv Gastroenterol. 2019; 12 (1756284819879565)Crossref Scopus (9) Google Scholar In liver failure, hemodialysis is efficient in eliminating small water-soluble toxins (e.g., urea, ammonia) but not in removing larger albumin-bound molecules (e.g., bilirubin, bile acids, medium-chain fatty acids, metabolites of aromatic amino acids and cytokines).20Zoica B.S. Deep A. Extracorporeal renal and liver support in pediatric acute liver failure [published online ahead of print June 5, 2020].Pediatr Nephrol. 2020; https://doi.org/10.1007/s00467-020-04613-4Crossref PubMed Scopus (0) Google Scholar,24Mitzner S.R. Stange J. Klammt S. et al.Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.Liver Transpl. 2000; 6: 277-286Crossref PubMed Scopus (584) Google Scholar, 25Mullen K.D. Treatment of hepatorenal syndrome: lessons from the MARS trial.Hepatology. 2002; 35: 492-493Crossref PubMed Scopus (0) Google Scholar, 26Best L.M. Freeman S.C. Sutton A.J. et al.Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis.Cochrane Database Syst Rev. 2019; 9: CD013103PubMed Google Scholar, 27Jain V. Dhawan A. Extracorporeal liver support systems in paediatric liver failure.J Pediatr Gastroenterol Nutr. 2017; 64: 855-863Crossref PubMed Scopus (1) Google Scholar, 28Bañares R. Ibáñez-Samaniego L. Torner J.M. et al.Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity.Therap Adv Gastroenterol. 2019; 12 (1756284819879565)Crossref Scopus (9) Google Scholar, 29Marangoni R. Bellati G. Castelli A. Romagnoli E. Development of high-efficiency molecular adsorbent recirculating system: preliminary report.Artif Organs. 2014; 38: 879-883Crossref PubMed Scopus (9) Google Scholar, 30Roth G.A. Faybik P. Hetz H. et al.MCP-1 and MIP3-alpha serum levels in acute liver failure and molecular adsorbent recirculating system (MARS) treatment: a pilot study.Scand J Gastroenterol. 2009; 44: 745-751Crossref PubMed Scopus (0) Google Scholar, 31Roth G.A. Nickl S. Lebherz-Eichinger D. et al.Lipocalin-2 serum levels are increased in acute hepatic failure.Transpl Proc. 2013; 45: 241-244Crossref PubMed Google Scholar Most liver failure–associated toxins such as bilirubin, fatty acids, hydrophobic bile acids, and nitric oxide use albumin as their transport protein and appear to be removed more effectively by albumin dialysis (Table 1).Table 1Examples of Albumin-Bound and Water-Soluble Substances Removing by MARS TherapyAlbumin-Bound SubstancesWater-Soluble Substances•Bilirubin•Bile acids•Tryptophan•Fatty acids (middle- and short-chained)•Aromatic amino acids•TNF-α•IL-6•Copper•Benzodiazepines•Manganese•Furancarboxylic acid•Indoxyl sulfate•Nitric oxide•Paracresol•ProtoporphyrinAmmoniaCreatinineUreaAbbreviations: TNF-α, tumor necrosis factor-alpha; IL-6, interleukin-6. Open table in a new tab Abbreviations: TNF-α, tumor necrosis factor-alpha; IL-6, interleukin-6. MARS therapy has been shown to reduce serum bilirubin, bile acids, ammonia, urea, and creatinine in patients with AoCLF32Stange J. Mitzner S.R. Risler T. et al.Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.Artif Organs. 1999; 23: 319-330Crossref PubMed Scopus (0) Google Scholar, 33Sorkine P. Ben Abraham R. Szold O. et al.Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure.Crit Care Med. 2001; 29: 1332-1336Crossref PubMed Google Scholar, 34Mitzner S.R. Klammt S. Peszynski P. et al.Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system.Ther Apher. 2001; 5: 417-422Crossref PubMed Scopus (0) Google Scholar and ALF,35Saliba F. Camus C. Durand F. et al.Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial.Ann Intern Med. 2013; 159: 522-531Crossref PubMed Scopus (141) Google Scholar, 36Hassanein T.I. Tofteng F. Brown Jr., R.S. et al.Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis.Hepatology. 2007; 46: 1853-1862Crossref PubMed Scopus (282) Google Scholar, 37Schmidt L.E. Wang L.P. Hansen B.A. Larsen F.S. Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial.Liver Transpl. 2003; 9: 290-297Crossref PubMed Scopus (0) Google Scholar and the improvement of these biochemical variables has been confirmed in multicenter randomized controlled trials (RCTs).35Saliba F. Camus C. Durand F. et al.Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial.Ann Intern Med. 2013; 159: 522-531Crossref PubMed Scopus (141) Google Scholar,36Hassanein T.I. Tofteng F. Brown Jr., R.S. et al.Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis.Hepatology. 2007; 46: 1853-1862Crossref PubMed Scopus (282) Google Scholar,38Bañares R. Nevens F. Larsen F.S. et al.Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial.Hepatology. 2013; 57: 1153-1162Crossref PubMed Scopus (0) Google Scholar,39Heemann U. Treichel U. Loock J. et al.Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.Hepatology. 2002; 36: 949-958Crossref PubMed Google Scholar Besides, plasma nitric oxide is bound to albumin as a nitrosothiol and is partly responsible for the hemodynamic profile observed in patients with liver failure. Several clinical investigations report the removal of nitric oxide by MARS,40Sen S. Davies N.A. Mookerjee R.P. et al.Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study.Liver Transpl. 2004; 10: 1109-1119Crossref PubMed Scopus (223) Google Scholar,41Guo L.M. Liu J.Y. Xu D.Z. et al.Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome.Liver Int. 2003; 23: 16-20Crossref PubMed Google Scholar which is one possible mechanism for improving hemodynamic parameters in those patients undergoing MARS treatment. Multiple studies showed improvement in hepatic encephalopathy.14Tsipotis E. Shuja A. Jaber B.L. Albumin dialysis for liver failure: a systematic review.Adv Chronic Kidney Dis. 2015; 22: 382-390Abstract Full Text Full Text PDF PubMed Google Scholar,42Vaid A. Chweich H. Balk E.M. Jaber B.L. Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis.Asaio j. 2012; 58: 51-59Crossref PubMed Scopus (54) Google Scholar This may be related to the removal of toxins as well as improvement in cerebral arterial flow.43Novelli G. Rossi M. Pretagostini R. et al.A 3-year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion.Liver Int. 2003; 23: 10-15Crossref PubMed Google Scholar,44Novelli G. Rossi M. Pretagostini M. et al.One hundred sixteen cases of acute liver failure treated with MARS.Transpl Proc. 2005; 37: 2557-2559Crossref PubMed Scopus (0) Google Scholar Liver failure is also associated with an imbalance of amino acid metabolism, resulting in low to normal plasma levels of glutamate, tryptophan, and branched-chain amino acids (leucine, isoleucine, and valine). However, most other amino acids (especially phenolic aromatic amino acids) are significantly accumulated.45Wittebole X. Hantson P. Use of the molecular adsorbent recirculating system (MARS™) for the management of acute poisoning with or without liver failure.Clin Toxicol (Phila). 2011; 49: 782-793Crossref PubMed Scopus (0) Google Scholar The degree of hepatic encephalopathy has been suggested to correlate with the ratio of branched-chain to phenolic aromatic amino acids. A significant reduction in total arterial amino acid concentration was noted during a single six-hour MARS treatment with a rise in branched-chain amino acid ratio to aromatic amino acids, which could potentially be beneficial.46Schmidt L.E. Tofteng F. Strauss G.I. Larsen F.S. Effect of treatment with the Molecular Adsorbents Recirculating System on arterial amino acid levels and cerebral amino acid metabolism in patients with hepatic encephalopathy.Scand J Gastroenterol. 2004; 39: 974-980Crossref PubMed Scopus (28) Google Scholar When compared with standard medical therapy, several studies demonstrated that removal of vasoactive substances and toxins by MARS resulted in the restoration of systemic vascular resistance, decreasing the need for vasopressor support, improved cerebral and systemic perfusion, improved hepatic encephalopathy, reduced portal hypertension and intracranial pressure, and pruritus relief in patients with liver failure.24Mitzner S.R. Stange J. Klammt S. et al.Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.Liver Transpl. 2000; 6: 277-286Crossref PubMed Scopus (584) Google Scholar,33Sorkine P. Ben Abraham R. Szold O. et al.Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure.Crit Care Med. 2001; 29: 1332-1336Crossref PubMed Google Scholar,34Mitzner S.R. Klammt S. Peszynski P. et al.Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system.Ther Apher. 2001; 5: 417-422Crossref PubMed Scopus (0) Google Scholar,36Hassanein T.I. Tofteng F. Brown Jr., R.S. et al.Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis.Hepatology. 2007; 46: 1853-1862Crossref PubMed Scopus (282) Google Scholar,37Schmidt L.E. Wang L.P. Hansen B.A. Larsen F.S. Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial.Liver Transpl. 2003; 9: 290-297Crossref PubMed Scopus (0) Google Scholar,40Sen S. Davies N.A. Mookerjee R.P. et al.Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study.Liver Transpl. 2004; 10: 1109-1119Crossref PubMed Scopus (223) Google Scholar,47Peszynski P. Klammt S. Peters E. Mitzner S. Stange J. Schmidt R. Albumin dialysis: single pass vs. recirculation (MARS).Liver. 2002; 22: 40-42Crossref PubMed Scopus (49) Google Scholar, 48Sauer I.M. Goetz M. Steffen I. et al.In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD).Hepatology. 2004; 39: 1408-1414Crossref PubMed Scopus (0) Google Scholar, 49Catalina M.V. Barrio J. Anaya F. et al.Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.Liver Int. 2003; 23: 39-43Crossref PubMed Google Scholar, 50Laleman W. Wilmer A. Evenepoel P. et al.Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure.Crit Care. 2006; 10: R108Crossref PubMed Scopus (184) Google Scholar, 51Sen S. Mookerjee R.P. Cheshire L.M. Davies N.A. Williams R. Jalan R. Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis.J Hepatol. 2005; 43: 142-148Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 52Schmidt L.E. Sørensen V.R. Svendsen L.B. Hansen B.A. Larsen F.S. Hemodynamic changes during a single treatment with the molecular adsorbents recirculating system in patients with acute-on-chronic liver failure.Liver Transpl. 2001; 7: 1034-1039Crossref PubMed Scopus (95) Google Scholar, 53Jalan R. Sen S. Steiner C. Kapoor D. Alisa A. Williams R. Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis.J Hepatol. 2003; 38: 24-31Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 54Schmidt L.E. Svendsen L.B. Sørensen V.R. Hansen B.A. Larsen F.S. Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure.Liver Transpl. 2001; 7: 709-712Crossref PubMed Scopus (90) Google Scholar, 55Parés A. Cisneros L. Salmerón J.M. et al.Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis.Am J Gastroenterol. 2004; 99: 1105-1110Crossref PubMed Scopus (0) Google Scholar, 56Bellmann R. Graziadei I.W. Feistritzer C. et al.Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis.Liver Transpl. 2004; 10: 107-114Crossref PubMed Scopus (0) Google Scholar, 57Koivusalo A.M. Teikari T. Höckerstedt K. Isoniemi H. Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy.Metab Brain Dis. 2008; 23: 387-398Crossref PubMed Scopus (24) Google Scholar, 58Pugliese F. Novelli G. Poli L. et al.Hemodynamic improvement as an additional parameter to evaluate the safety and tolerability of the mol