Albumin-bound toxins accumulate in liver failure, and are believed to contribute to
the development of the associated end-organ dysfunctions (kidney, circulation,
brain). The scavenging functions of albumin are utilized in albumin dialysis for
toxin removal. The Molecular Adsorbents Recirculating System (MARS) is an
extracorporeal liver support device based on dialysis across an albumin-impregnated
membrane, using 20% albumin as dialysate. Charcoal and anion exchange resin columns
in the circuit help cleanse and regenerate the dialysate. Clinical studies over the
last decade have demonstrated proven reduction in hyperbilirubinaemia, along with an
improvement in hepatic encephalopathy, systemic haemodynamics and renal function in
liver failure patients, as well as apparent improvement in survival. However, the
specific mechanisms underlying these observed clinical changes are as yet unclear.
The results of larger controlled clinical trials, as well as studies investigating
the pathophysiological basis of its effect, are awaited.
Jalan R, Williams R.Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif2002; 20: 252-261.
3.
Sen S, Williams R, Jalan R.The pathophysiological basis of acute-on-chronic liver failure. Liver2002; 22: 5-13.
4.
Arroyo V.Review article: albumin in the treatment of liver diseases - new features
of a classical treatment. Aliment Pharmacol Ther2002; 16: 1-5.
5.
Ruiz-del-Arbol L, Monescillo A, Jimenez W, Garcia-Plaza A, Arroyo V, Rodes J.Paracentesis-induced circulatory dysfunction: mechanism and effect on
hepatic hemodynamics in cirrhosis. Gastroenterology1997; 113: 579-586.
6.
Gines A, Fernandez-Esparrach G, Monescillo A, et al.Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic
patients with ascites treated by paracentesis. Gastroenterology1996; 111: 1002-1010.
7.
Sort P, Navasa M, Arroyo V, et al.Effect of intravenous albumin on renal impairment and mortality in patients
with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med1999; 341: 403-409.
8.
Duvoux C, Zanditenas D, Hezode C, et al.Effects of noradrenalin and albumin in patients with type I hepatorenal
syndrome: a pilot study. Hepatology2002; 36: 374-380.
9.
Ortega R, Gines P, Uriz J, et al.Terlipressin therapy with and without albumin for patients with hepatorenal
syndrome: results of a prospective, nonrandomized study. Hepatology2002; 36: 941-948.
10.
Curry S, Mandelkow H, Brick P, Franks N.Crystal structure of human serum albumin complexed with fatty acid reveals
an asymmetric distribution of binding sites. Nat Struct Biol1998; 5: 827-835.
11.
Evans TW.Review article: albumin as a drug biological effects of albumin unrelated
to oncotic pressure. Aliment Pharmacol Ther2002; 16: 6-11.
12.
Awad SS, Rich PB, Kolla S, et al.Characteristics of an albumin dialysate hemodiafiltration system for the
clearance of unconjugated bilirubin. Asaio J1997; 43: M745-M749.
13.
Awad SS, Sawada S, Soldes OS, et al.Can the clearance of tumor necrosis factor alpha and interleukin 6 be
enhanced using an albumin dialysate hemodiafiltration system?Asaio J1999; 45: 47-49.
14.
Awad SS, Swaniker F, Magee J, Punch J, Bartlett RH.Results of a phase I trial evaluating a liver support device utilizing
albumin dialysis. Surgery2001; 130: 354-362.
15.
Jalan 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 Hepatol2003; 38: 24-31.
16.
Stange J, Mitzner S.A carrier-mediated transport of toxins in a hybrid membrane. Safety barrier
between a patient’s blood and a bioartificial liver. Int J Artif Organs1996; 19: 677-691.
17.
Stange J, Ramlow W, Mitzner S, Schmidt R, Klinkmann H.Dialysis against a recycled albumin solution enables the removal of
albumin-bound toxins. Artif Organs1993; 17: 809-813.
18.
Hughes R, Ton HY, Langley P, et al.Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver
failure. Part II: in vivo evaluation. Artif Organs1979; 3: 23-26.
19.
Stange J, Mitzner S, Ramlow W, Gliesche T, Hickstein H, Schmidt R.A new procedure for the removal of protein bound drugs and toxins. Asaio J1993; 39: M621-M625.
20.
Mitzner SR, Klammt S, Peszynski P, et al.Improvement of multiple organ functions in hepatorenal syndrome during
albumin dialysis with the molecular adsorbent recirculating system. Ther Apher2001; 5: 417-422.
21.
Sorkine 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 Med2001; 29: 1332-1336.
22.
Stange J, Mitzner SR, Risler T, et al.Molecular adsorbent recycling system (MARS): clinical results of a new
membrane-based blood purification system for bioartificial liver support. Artif Organs1999; 23: 319-330.
23.
Schmidt LE, Svendsen LB, Sorensen VR, Hansen BA, Larsen FS.Cerebral blood flow velocity increases during a single treatment with the
molecular adsorbents recirculating system in patients with acute on chronic
liver failure. Liver Transpl2001; 7: 709-712.
24.
Schmidt LE, Sorensen VR, Svendsen LB, Hansen BA, Larsen FS.Hemodynamic changes during a single treatment with the molecular adsorbents
recirculating system in patients with acute-on-chronic liver failure. Liver Transpl2001; 7: 1034-1039.
25.
Mitzner SR, Stange J, Klammt S, et al.Improvement of hepatorenal syndrome with extracorporeal albumin dialysis
MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl2000; 6: 277-286.
26.
Stange J, Mitzner SR, Klammt S, et al.Liver support by extracorporeal blood purification: a clinical observation. Liver Transpl2000; 6: 603-613.
27.
Heemann U, Treichel U, Loock J, et al.Albumin dialysis in cirrhosis with superimposed acute liver injury: a
prospective, controlled study. Hepatology2002; 36: 949-958.
28.
Novelli G, Rossi M, Pretagostini R, et al.MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of
acute liver failure. Liver2002; 22: 43-47.
29.
Isoniemi H.Current indications for albumin dialysis: acute hepatic failure. In 4th International Symposium on Albumin Dialysis in Liver
Disease, Rostock-Warnemunde, September 2002.
30.
Abraham RB, Szold O, Merhav H, et al.Rapid resolution of brain edema and improved cerebral perfusion pressure
following the molecular adsorbent recycling system in acute liver failure patients. Transplant Proc2001; 33: 2897-2899.
31.
Schmidt LE, Wang LP, Hansen BA, Larsen FS.Systemic hemodynamic effects of treatment with the molecular adsorbents
recirculating system in patients with hyperacute liver failure: a
prospective controlled trial. Liver Transpl2003; 9: 290-297.
32.
Lamesch P, Jost U, Schreiter D, et al.Molecular adsorbant recirculating system in patients with liver failure. Transplant Proc2001; 33: 3480-3482.
33.
Manz T, Ochs A, Bisse E, Strey C, Grotz W.Liver support - a task for nephrologists? Extracorporeal treatment of a
patient with fulminant Wilson crisis. Blood Purif2003; 21: 232-236.
34.
Sen S, Felldin M, Steiner C, et al.Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for
acute Wilson’s disease. Liver Transpl2002; 8: 962-967.
35.
Kreymann B, Seige M, Schweigart U, Kopp KF, Classen M.Albumin dialysis: effective removal of copper in a patient with fulminant
Wilson disease and successful bridging to liver transplantation: a new
possibility for the elimination of protein-bound toxins. J Hepatol1999; 31: 1080-1085.
36.
McIntyre CW, Fluck RJ, Freeman JG, Lambie SH.Use of albumin dialysis in the treatment of hepatic and renal dysfunction
due to paracetamol intoxication. Nephrol Dial Transplant2002; 17: 316-317.
37.
Siewert-Delle A, Henriksson BA, Baeckmann L.Albumin dialysis with the MARS for a patient with acute liver failure due
to paracetamol intoxication: a case report. Z Gastroenterol2001; 39: 48-48.
38.
Shi Y, He J, Chen S, et al.MARS: optimistic therapy method in fulminant hepatic failure secondary to
cytotoxic mushroom poisoning - a case report. Liver2002; 22: 78-80.
39.
Catalina MV, Nunez O, Ponferrada A, et al.Liver failure due to mushroom poisoning: clinical course and new treatment perspectives. Gastroenterol Hepatol2003; 26: 417-420.
40.
Novelli G, Rossi M, Pretagostini R, et al.Use of MARS in the treatment of acute liver failure: preliminary
monocentric experience. Transplant Proc2001; 33: 1942-1944.
41.
Stange J, Hassanein TI, Mehta R, Mitzner SR, Bartlett RH.The molecular adsorbents recycling system as a liver support system based
on albumin dialysis: a summary of preclinical investigations, prospective,
randomized, controlled clinical trial, and clinical experience from 19 centers. Artif Organs2002; 26: 103-110.
42.
Kellersmann R, Gassel HJ, Buhler C, Thiede A, Timmermann W.Application of Molecular Adsorbent Recirculating System in patients with
severe liver failure after hepatic resection or transplantation: initial
single-centre experiences. Liver2002; 22: 56-58.
43.
Mullhaupt B, Kullak-Ublick GA, Ambuhl P, et al.First clinical experience with Molecular Adsorbent Recirculating System
(MARS) in six patients with severe acute on chronic liver failure. Liver2002; 22: 59-62.
44.
Delafosse B, Garnier E, Dumortier J, Boillot O.Edouard Herriot experience with the MARS in 5 patients experiencing hepatic failure. Z Gastroenterol2001; 39: 38-38.
45.
Sturm E, Franssen CF, Gouw A, et al.Extracorporeal albumin dialysis (MARS) improves cholestasis and normalizes
low apo A-I levels in a patient with benign recurrent intrahepatic
cholestasis (BRIC). Liver2002; 22: 72-75.
46.
Mullhaupt B, Kullak-Ublick GA, Ambuhl PM, Stocker R, Renner EL.Successful use of the Molecular Adsorbent Recirculating System (MARS) in a
patient with primary biliary cirrhosis (PBC) and treatment refractory pruritus. Hepatol Res2003; 25: 442-446.
47.
Doria C, Mandala L, Smith J, et al.Effect of molecular adsorbent recirculating system in hepatitis C
virus-related intractable pruritus. Liver Transpl2003; 9: 437-443.
48.
Sen S, Jalan R, Morris EC, Steiner C, Mackinnon S, Williams R.Reversal of severe cholestasis caused by chronic graft-versus-host disease
with the MARS liver-support device. Transplantation2003; 75: 1766-1767.
49.
Notohamiprodjo M, Banayosy A, Kizner L, Schuller V, Korfer R.One year experience with MARS therapy in patients with multiorgan failure
in Cardiac Center Bad Oyenhausen. Z Gastroenterol2001; 39: 51-51.
50.
Mitzner SR, Stange J, Klammt S, Peszynski P, Schmidt R, Noldge-Schomburg G.Extracorporeal detoxification using the molecular adsorbent recirculating
system for critically ill patients with liver failure. J Am Soc Nephrol2001; 12: S75-S82.
51.
Sen S, Mookerjee RP, Davies NA, Williams R, Jalan R.Review article: the Molecular Adsorbents Recirculating System (MARS) in
liver failure. Aliment Pharmacol Ther2002; 16: 32-38.
52.
Sen S, Davies NA, Mookerjee RP, Cheshire L, Williams R, Jalan R.Pathophysiological basis of clinical changes in acute-on-chronic liver
failure following treatment with MARS: a randomized evaluation. In 4th International Symposium on Albumin Dialysis in Liver
Disease, Rostock -Warnemunde, September 2002.
53.
Sen S, Ratnaraj N, Davies NA, et al.Treatment of phenytoin toxicity by the molecular adsorbents recirculating
system (MARS). Epilepsia2003; 44: 265-267.
