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Molecular Absorbent Recirculating System

Molecular Absorbent Recirculating System

Article Author:
Siva Naga Yarrarapu
Article Editor:
Devang Sanghavi
8/10/2020 5:42:59 PM
For CME on this topic:
Molecular Absorbent Recirculating System CME
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Molecular Absorbent Recirculating System


Liver failure is a medical emergency carrying a high mortality rate. It presents in an individual with normal liver function as acute liver failure(ALF), and in an individual with chronic liver disease either as ‘acute on chronic’ liver failure(AOCF) or decompensated end-stage liver disease. Though the etiology may be different, all the types of liver failure result in the accumulation of toxic metabolites in the body that causes end-organ dysfunction, eventually culminating in multi-organ failure and death.[1] Liver support devices/systems play a significant role in the management of ALF and AOCF, as they are likely reversible and these systems replicate the detoxifying function of the liver, until the endemic function of the liver recovers. Though liver transplantation is the only potent therapeutic option for end-stage liver disease, a matching liver transplant may not be immediately accessible. Also, by the time the donor graft becomes available, the patient may be having multi-organ failure rendering it unsuitable for transplantation. Liver support systems can be useful in such scenarios as they can stabilize the patient’s health till the time transplant becomes available or he/she is eligible for transplantation.[2] Liver support systems group into artificial systems and the bioartificial systems.[3] This review article focuses on the Molecular Adsorbent Recirculating System (MARS), an artificial system that has been comprehensively used since 1998 when it was made accessible for clinical usage.[4] 

Issues of Concern


Molecular adsorbent recirculating system (MARS) is an extracorporeal hepatic support system that integrates the mechanisms of dialysis, ultrafiltration, and adsorption.[5] It involves the elimination of toxins from the blood, albumin-bound as well as water-soluble toxins, thus cleansing the body of toxic catabolites accumulated from hepatic failure.[6]

MARS exploits the usage of three different circuits- a blood circuit that utilizes hemodialyzer (MARS FLUX dialyzer), an albumin circuit that contains an anionic exchange column, and an activated charcoal adsorber, and a dialysate circuit that utilizes conventional dialyzer. Of the two pumps that drive the system, one pump drives the blood circuit and is catered by the standard hemodialyzer (HD)/conventional veno-venous hemofiltration (CVVH) equipment. The closed-loop albumin circuit interconnects the blood and dialysate circuits and is controlled by the pump provided by the MARS monitor.[7][8][9]

Vascular access is obtained through a double lumen catheter either from the internal jugular vein, subclavian vein, or the femoral vein. Blood runs through the MARS FLUX dialyzer at a flow rate controlled between 150 TO 250 ml/min and its dialysis done against an albumin solution across an albumin permeated membrane. 600 ml of 10 to 20% albumin dialysate is used to fill the circuit and is run in a direction opposite to the blood flow across the hemodialyzer.[10][9]

Based on the concepts of protein affinity and the difference in the concentration gradient of the solutes between the two compartments of the MARS FLUX dialyzer, the highly permeable membrane facilitates the diffusion of protein-bound and water-soluble toxins into the albumin dialysate. Albumin in the dialysate solution has free binding sites, and its affinity towards hydrophobic toxins in the circulating blood pulls them across the membrane and is thus retained by the dialysate. The MARS flux membrane doesn’t allow proteins larger than 50 kDa (example: growth factors) to diffuse across the membrane.[7][11]

The albumin dialysate then circulates through an anionic exchanger and an activated carbon adsorber, which facilitates the removal of protein-bound toxins through the process of adsorption. Subsequently, the solution undergoes another cycle of detoxification where it is dialyzed against bicarbonate buffered dialysate in a diaFLUX dialyzer to clear it of water-soluble toxins and thereby, the purified albumin dialysate recirculates into the blood circuit for reuse.[10]

Unfractionated heparin is administered during the therapy at a dosage of 1500 to 4000 IU/hour for effective anticoagulation. The monitoring of heparin therapy is via activated clotting time (ACT), maintained between 160 and 200 seconds.[12][13] Therapy takes place in sessions, and typically, each session of MARS treatment takes around 6 TO 8 hours.[10]

Clinical Significance

MARS assists in attenuation of the clinical manifestations of liver failure through the removal of accumulated bilirubin, bile acids, ammonia, aromatic amino acids, pro-inflammatory cytokines, and nitric oxide, which carry implications in the pathophysiology of hepatic encephalopathy, hepatorenal syndrome, and hyperdynamic circulatory failure. By removal of the vasoactive agents (NO and inflammatory cytokines), MARS assists in increasing the systemic vascular resistance and mean arterial pressure, thus, stabilizing the circulation. Bilirubin and bile acids are hepatotoxic and have the potential to cause hepatocyte necrosis. Therefore, by removing them from the body, MARS serves to halt the process of liver damage temporarily. MARS has also been associated with improvement in liver function, as evidenced by an increase in the synthesis of factor VII, antithrombin III, and prothrombin.[14][4][8]

MARS has demonstrated an improvement in short term survival in patients with acute on chronic liver failure in a few studies. In a randomized controlled trial conducted by Mitzner et al., out of the 13 patients with type 1 hepatorenal syndrome, eight received treatment with MARS and five with hemodiafiltration (HDF). MARS correlates with a 68% survival impact compared to 0% survival in patients treated with HDF. There was a significant improvement in hemodynamic status, decreased bilirubin, improved biochemistry, and prothrombin time index. The RELIEF trial saw the participation of 189 patients with ACLF. Compared to the patients treated with standard therapy, a greater percentage of patients treated with MARS had a significant improvement in hepatic encephalopathy (38.2% vs. 62.5%, respectively). Hepatic encephalopathy improved from grade III-IV to grade 0-I, and the study was statistically significant (p=0.07). Several studies assessing the impact of MARS on ACLF patients were associated with a decrease in hepatic encephalopathy and improvement of Child-Pugh scores. At present, the FDA has approved the use of MARS for HE improvement in patients with chronic liver disease.[15][16][9][17][18] There is relatively less information on the benefit of MARS in acute liver failure. Even though there is uncertainty about the survival benefit in ALF, MARS has linked with the betterment of hepatic encephalopathy, hemodynamic status, and reduction of bilirubin.[9][7][2]

INDICATIONS [10][19][20][21][22][5][14]

Indications for MARS usage includes:

1.Acute Liver Failure (ALF)

MARS is used in ALF, provided there is a failure of disease resolution despite maximal medical treatment and that the etiology can be treated. ALF is potentially reversible, and by stabilizing the patient, MARS provides time for recovery and also serves as a ''bridge to transplantation'', if a liver transplant is needed.

Causes of ALF where MARS has been used include:

  • Acute alcoholic hepatitis
  • Fulminant viral hepatitis: hepatitis B, hepatitis C
  • Drugs: acetaminophen, allopurinol,[23] chromium,[24] and copper[25]
  • Natural toxins: Amanita phalloides

2. Acute on Chronic Liver Failure (rehabilitation/bridge to transplantation)

3. Decompensated End-Stage Liver Disease (bridge to transplantation)

4. Acute Decompensation of the liver causing: hepatic encephalopathy (grade ≥ 2), hepatorenal syndrome

5. Intractable pruritus despite maximal medical treatment. Causes include: primary biliary cirrhosis, primary sclerosis cholangitis, chronic viral hepatitis, alcoholic liver disease, nonalcoholic hepatitis

6. Post-transplantation liver failure

7. Liver failure following hepatectomy/severe mechanical trauma

8. Poisoning with albumin-bound drugs unrelated to liver failure: phenytoin,[26] theophylline,[27] and lamotrigine[28]


MARS has a very good safety profile and is tolerated well by the patients. Except for the fact that MARS is expensive, patients have no specific complaints regarding the procedure. Thrombocytopenia has been documented during the therapy, but it is mild and poses no significant threat to the patient. The risks associated with MARS are the same as the ones with conventional hemodialysis and requires the use of anticoagulants to prevent coagulation activation during the procedure. In patients with end-stage liver disease, the risk of thrombosis and bleeding significantly increases, and hence, the use of anticoagulation is of utmost importance. For this, unfractionated heparin is the anticoagulant of choice, as evidenced by most clinical trials.[19][10][7]

MARS is relatively contraindicated if there is an increased risk of coagulopathy (example: disseminated intravascular coagulation) i.e., when platelets are below 50,000/microlitre of blood or when the INR is greater than 2.3. Uncontrolled sepsis or uncontrolled hemorrhage are also prohibitions to the use of MARS and are considered as relative contraindications.[20] 

MARS has been so successful in attenuating the symptomatology and biochemical parameters of liver failure that it is now in use for a wide range of indications. The usage of MARS has been increasing ever since its inception and has received considerations from different sub-specialties of medicine. There are no large clinical trials proving its efficacy as far as mortality benefit is concerned; however, there are numerous case reports, case series, and underpowered studies showing its effectiveness in the settings described above. However, it certainly a costly therapy requiring highly specific skill set and expertise to operate available only at certain centers which offer transplant. Larger randomized control trials with effective endpoints are necessary to justify its use at a bigger scale and expanding its indication. Till we have better data regarding its efficacy, this therapy will be a highly specialized therapy limited to certain small centers.[29][9][14]

Nursing, Allied Health, and Interprofessional Team Interventions

MARS is a complex medical therapy and requires effective communication and teamwork between the gastroenterologist, critical care specialist, transplant surgeon, nephrologist, and healthcare workers in the ICU to resuscitate the patient and improve patient outcomes.


[1] Williams R, The elusive goal of liver support--quest for the Holy Grail. Clinical medicine (London, England). 2006 Sep-Oct;     [PubMed PMID: 17080897]
[2] Sen S,Mookerjee RP,Davies NA,Williams R,Jalan R, Review article: the molecular adsorbents recirculating system (MARS) in liver failure. Alimentary pharmacology     [PubMed PMID: 12423451]
[3] Podoll AS,DeGolovine A,Finkel KW, Liver support systems--a review. ASAIO journal (American Society for Artificial Internal Organs : 1992). 2012 Sep-Oct;     [PubMed PMID: 22820917]
[4] Mitzner SR, Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS). Annals of hepatology. 2011 May;     [PubMed PMID: 21566251]
[5] Mielnicki W,Dyla A,Karczewski M, Clinical effectiveness of MARS treatment - multidirectional analysis of positive clinical response to treatment. Clinical and experimental hepatology. 2019 Nov;     [PubMed PMID: 31893237]
[6] Stange J,Mitzner SR,Risler T,Erley CM,Lauchart W,Goehl H,Klammt S,Peszynski P,Freytag J,Hickstein H,Löhr M,Liebe S,Schareck W,Hopt UT,Schmidt R, Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support. Artificial organs. 1999 Apr;     [PubMed PMID: 10226696]
[7] García Martínez JJ,Bendjelid K, Artificial liver support systems: what is new over the last decade? Annals of intensive care. 2018 Nov 15;     [PubMed PMID: 30443736]
[8] Mitzner SR,Stange J,Klammt S,Peszynski P,Schmidt R,Nöldge-Schomburg G, Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. Journal of the American Society of Nephrology : JASN. 2001 Feb;     [PubMed PMID: 11251037]
[9] Kapoor D, Molecular adsorbent recirculating system: albumin dialysis-based extracorporeal liver assist device. Journal of gastroenterology and hepatology. 2002 Dec;     [PubMed PMID: 12472950]
[10] Boyle M,Kurtovic J,Bihari D,Riordan S,Steiner C, Equipment review: the molecular adsorbents recirculating system (MARS). Critical care (London, England). 2004 Aug;     [PubMed PMID: 15312211]
[11] Sen S,Jalan R,Williams R, Liver failure: basis of benefit of therapy with the molecular adsorbents recirculating system. The international journal of biochemistry     [PubMed PMID: 12798344]
[12] Laleman W,Wilmer A,Evenepoel P,Elst IV,Zeegers M,Zaman Z,Verslype C,Fevery J,Nevens F, 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. Critical care (London, England). 2006;     [PubMed PMID: 16859530]
[13] Parés A,Deulofeu R,Cisneros L,Escorsell A,Salmerón JM,Caballería J,Mas A, Albumin dialysis improves hepatic encephalopathy and decreases circulating phenolic aromatic amino acids in patients with alcoholic hepatitis and severe liver failure. Critical care (London, England). 2009;     [PubMed PMID: 19175915]
[14] Mitzner SR,Stange J,Klammt S,Peszynski P,Schmidt R, Albumin dialysis using the molecular adsorbent recirculating system. Current opinion in nephrology and hypertension. 2001 Nov;     [PubMed PMID: 11706305]
[15] Gerth HU,Pohlen M,Thölking G,Pavenstädt H,Brand M,Hüsing-Kabar A,Wilms C,Maschmeier M,Kabar I,Torner J,Pavesi M,Arroyo V,Banares R,Schmidt HHJ, Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis. Critical care medicine. 2017 Oct;     [PubMed PMID: 28640024]
[16] Bañares R,Nevens F,Larsen FS,Jalan R,Albillos A,Dollinger M,Saliba F,Sauerbruch T,Klammt S,Ockenga J,Pares A,Wendon J,Brünnler T,Kramer L,Mathurin P,de la Mata M,Gasbarrini A,Müllhaupt B,Wilmer A,Laleman W,Eefsen M,Sen S,Zipprich A,Tenorio T,Pavesi M,Schmidt HH,Mitzner S,Williams R,Arroyo V, Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology (Baltimore, Md.). 2013 Mar;     [PubMed PMID: 23213075]
[17] Mitzner SR,Stange J,Klammt S,Risler T,Erley CM,Bader BD,Berger ED,Lauchart W,Peszynski P,Freytag J,Hickstein H,Loock J,Löhr JM,Liebe S,Emmrich J,Korten G,Schmidt R, Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 May;     [PubMed PMID: 10827226]
[18] Leise MD,Poterucha JJ,Kamath PS,Kim WR, Management of hepatic encephalopathy in the hospital. Mayo Clinic proceedings. 2014 Feb;     [PubMed PMID: 24411831]
[19] Saliba F, The Molecular Adsorbent Recirculating System (MARS) in the intensive care unit: a rescue therapy for patients with hepatic failure. Critical care (London, England). 2006 Feb;     [PubMed PMID: 16542471]
[20] Jalan R,Sen S,Williams R, Prospects for extracorporeal liver support. Gut. 2004 Jun;     [PubMed PMID: 15138219]
[21] Tan HK, Molecular adsorbent recirculating system (MARS). Annals of the Academy of Medicine, Singapore. 2004 May;     [PubMed PMID: 15175774]
[22] Hanish SI,Stein DM,Scalea JR,Essien EO,Thurman P,Hutson WR,Bartlett ST,Barth RN,Scalea TM, Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure. Annals of surgery. 2017 Oct;     [PubMed PMID: 28692474]
[23] Fagugli RM,Gentile G,Ferrara G,Brugnano R, Acute renal and hepatic failure associated with allopurinol treatment. Clinical nephrology. 2008 Dec;     [PubMed PMID: 19049711]
[24] Prokurat S,Grenda R,Lipowski D,Kaliciński P,Migdal M, MARS procedure as a bridge to combined liver-kidney transplantation in severe chromium-copper acute intoxication: a paediatric case report. Liver. 2002;     [PubMed PMID: 12220311]
[25] 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. Journal of hepatology. 1999 Dec;     [PubMed PMID: 10604583]
[26] Sen S,Ratnaraj N,Davies NA,Mookerjee RP,Cooper CE,Patsalos PN,Williams R,Jalan R, Treatment of phenytoin toxicity by the molecular adsorbents recirculating system (MARS). Epilepsia. 2003 Feb;     [PubMed PMID: 12558586]
[27] Korsheed S,Selby NM,Fluck RJ, Treatment of severe theophylline poisoning with the molecular adsorbent recirculating system (MARS). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2007 Mar;     [PubMed PMID: 17164319]
[28] Mecarelli O,Pulitano P,Mingoia M,Ferretti G,Rossi M,Berloco PB,Muda AO, Acute hepatitis associated with lamotrigine and managed with the molecular adsorbents recirculating system (Mars). Epilepsia. 2005 Oct;     [PubMed PMID: 16190944]
[29] Di Campli C,Zileri Dal Verme L,Andrisani MC,Armuzzi A,Candelli M,Gaspari R,Gasbarrini A, Advances in extracorporeal detoxification by MARS dialysis in patients with liver failure. Current medicinal chemistry. 2003 Feb;     [PubMed PMID: 12570706]