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Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts

  • Narrative Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert’s recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts’ statements may help careful patient selection and better treatment modalities.

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Abbreviations

ABT:

Albumin-bound toxin

ACLF:

Acute-on-chronic liver failure

ALF:

Acute liver failure

DAMP:

Damage-associated molecular proteins

HE:

Hepatic encephalopathy

HLI:

Hypoxic liver injury

HSA:

Human serum albumin

ICU:

Intensive care unit

LTx:

Liver transplantation

MARS™:

Molecular Adsorbent Recirculating System

MELD:

Model of end-stage liver disease (score)

MOST:

Multiorgan support organ support therapies

PHLF:

Post-hepatectomy liver failure

RCA:

Regional citrate anticoagulation

HVPE:

High volume plasma exchange

RCT:

Randomized controlled trial

SMT:

Standard medical therapy

VAS:

Visual analogue scale

References

  1. Saliba F, Samuel D (2015) Artificial liver support: a real step forward. Minerva Med 106:35–43

    CAS  PubMed  Google Scholar 

  2. Camus C, Locher C, Saliba F, Goubaux B, Bonadona A, Lavayssiere L, Paugam C, Quinart A, Barbot O, Dharancy S, Delafosse B, Pichon N, Barraud H, Galbois A, Veber B, Cayot S, Souche B (2020) Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: a national multicenter study. JGH Open Open Access J Gastroenterol Hepatol 4:757–763

    Google Scholar 

  3. Kanjo A, Ocskay K, Gede N, Kiss S, Szakács Z, Párniczky A, Mitzner S, Stange J, Hegyi P, Molnár Z (2021) Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis. Sci Rep 11:4189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Alshamsi F, Alshammari K, Belley-Cote E, Dionne J, Albrahim T, Albudoor B, Ismail M, Al-Judaibi B, Baw B, Subramanian RM, Steadman R, Galusca D, Huang DT, Nanchal R, Al Quraini M, Yuan Y, Alhazzani W (2020) Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials. Intensive Care Med 46:1–16

    Article  PubMed  Google Scholar 

  5. Tandon R, Froghi S (2021) Artificial liver support systems. J Gastroenterol Hepatol 36:1164–1179

    Article  CAS  PubMed  Google Scholar 

  6. Ocskay K, Kanjo A, Gede N, Szakács Z, Pár G, Erőss B, Stange J, Mitzner S, Hegyi P, Molnár Z (2021) Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis. Ann Intensive Care 11(1):10. https://doi.org/10.1186/s13613-020-00795-0

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ronco C, Ricci Z, Husain-Syed F (2019) From multiple organ support therapy to extracorporeal organ support in critically ill patients. Blood Purif 48:99–105

    Article  PubMed  Google Scholar 

  8. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bernardi M, Angeli P, Claria J, Moreau R, Gines P, Jalan R, Caraceni P, Fernandez J, Gerbes AL, O’Brien AJ, Trebicka J, Thevenot T, Arroyo V (2020) Albumin in decompensated cirrhosis: new concepts and perspectives. Gut 69:1127–1138

    Article  CAS  PubMed  Google Scholar 

  10. Peters TJ (1995) All about albumin: biochemistry, genetics, and medical applications. Academic Press, San Diego

    Google Scholar 

  11. Quinlan GJ, Martin GS, Evans TW (2005) Albumin: biochemical properties and therapeutic potential. Hepatology 41:1211–1219

    Article  CAS  PubMed  Google Scholar 

  12. Sleep D (2015) Albumin and its application in drug delivery. Expert Opin Drug Deliv 12:793–812

    Article  CAS  PubMed  Google Scholar 

  13. Merlot AM, Kalinowski DS, Richardson DR (2014) Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol 5:299

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bern M, Sand KM, Nilsen J, Sandlie I, Andersen JT (2015) The role of albumin receptors in regulation of albumin homeostasis: implications for drug delivery. J Control Release Off J Control Release Soc 211:144–162

    Article  CAS  Google Scholar 

  15. Galis Z, Ghitescu L, Simionescu M (1988) Fatty acids binding to albumin increases its uptake and transcytosis by the lung capillary endothelium. Eur J Cell Biol 47:358–365

    CAS  PubMed  Google Scholar 

  16. Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J (2016) High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol 64:69–78

    Article  PubMed  Google Scholar 

  17. O’Grady JG, Gimson AE, O’Brien CJ, Pucknell A, Hughes RD, Williams R (1988) Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 94:1186–1192

    Article  PubMed  Google Scholar 

  18. Mitzner S, Klammt S, Stange J, Schmidt R (2006) Albumin regeneration in liver support-comparison of different methods. Ther Apher Dial Off Peer-Rev J Int Soc Apher Jpn Soc Apher Jpn Soc Dial Ther 10:108–117

    CAS  Google Scholar 

  19. Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, Barange K, Perrigault PF, Belnard M, Ichai P, Samuel D (2013) Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med 159:522–531

    Article  PubMed  Google Scholar 

  20. Ilonen I, Koivusalo AM, Repo H, Höckerstedt K, Isoniemi H (2008) Cytokine profiles in acute liver failure treated with albumin dialysis. Artif Organs 32:52–60

    CAS  PubMed  Google Scholar 

  21. Schmidt LE, Tofteng F, Strauss GI, Larsen FS (2004) 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 39:974–980

    Article  CAS  PubMed  Google Scholar 

  22. Kantola T, Koivusalo AM, Höckerstedt K, Isoniemi H (2008) The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients. Transpl Int 21:857–866

    Article  PubMed  Google Scholar 

  23. Camus C, Lavoué S, Gacouin A, Compagnon P, Boudjéma K, Jacquelinet C, Thomas R, Le Tulzo Y (2009) Liver transplantation avoided in patients with fulminant hepatic failure who received albumin dialysis with the molecular adsorbent recirculating system while on the waiting list: impact of the duration of therapy. Ther Apher Dial Off Peer-Rev J Int Soc Apher Jpn Soc Apher Jpn Soc Dial Ther 13:549–555

    CAS  Google Scholar 

  24. Gerth HU, Pohlen M, Thölking G, Pavenstädt H, Brand M, Wilms C, Hüsing-Kabar A, Görlich D, Kabar I, Schmidt HH (2017) Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: results from a case-control study. PLoS One 12:e0175529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. MacDonald AJ, Subramanian RM, Olson JC, Speiser JL, Durkalski-Mauldin VL, Abraldes JG, Bigam DL, Flynn MM, Rapaka B, Shropshire BM, Vora RS, Karvellas CJ (2022) Use of the molecular adsorbent recirculating system in acute liver failure: results of a multicenter propensity score-matched study. Crit Care Med 50(2):286–295

  26. Arroyo V, Moreau R, Jalan R (2020) Acute-on-chronic liver failure. N Engl J Med 382:2137–2145

    Article  CAS  PubMed  Google Scholar 

  27. Sen S, Davies NA, Mookerjee RP, Cheshire LM, Hodges SJ, Williams R, Jalan R (2004) Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 10:1109–1119

    Google Scholar 

  28. Catalina MV, Barrio J, Anaya F, Salcedo M, Rincón D, Clemente G, Bañares R (2003) Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure. Liver Int Off J Int Assoc Study Liver 23(Suppl 3):39–43

    Article  CAS  Google Scholar 

  29. Laleman W, Wilmer A, Evenepoel P, Elst IV, Zeegers M, Zaman Z, Verslype C, Fevery J, Nevens F (2006) 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 (Lond, Engl) 10:R108

    Article  Google Scholar 

  30. Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R (2005) Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol 43:142–148

    Article  CAS  PubMed  Google Scholar 

  31. Stadlbauer V, Krisper P, Aigner R, Haditsch B, Jung A, Lackner C, Stauber RE (2006) Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure. Crit Care (Lond, Engl) 10:R169

    Article  Google Scholar 

  32. Banares R, Ibanez-Samaniego L, Torner JM, Pavesi M, Olmedo C, Catalina MV, Albillos A, Larsen FS, Nevens F, Hassanein T, Schmidt H, Heeman U, Jalan R, Moreau R, Arroyo V (2019) Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity. Ther Adv Gastroenterol 12:1–12

    Article  Google Scholar 

  33. Khuroo MS, Khuroo MS, Farahat KL (2004) Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 10:1099–1106

    Google Scholar 

  34. Liu Y, Kang YZ, Xia WZ, Zhou HC, Wang Y, Gao Y (2009) Artificial and bioartificial liver support systems for acute and acute-on-chronic liver failure: a meta-analysis. Nan Fang Yi Ke Da Xue Xue Bao 29:1529–1532

    PubMed  Google Scholar 

  35. Stutchfield BM, Simpson K, Wigmore SJ (2011) Systematic review and meta-analysis of survival following extracorporeal liver support. Br J Surg 98:623–631

    Article  CAS  PubMed  Google Scholar 

  36. Vaid A, Chweich H, Balk EM, Jaber BL (2012) Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J 58:51–59

    Article  CAS  PubMed  Google Scholar 

  37. Zheng Z, Li X, Li Z, Ma X (2013) Artificial and bioartificial liver support systems for acute and acute-on-chronic hepatic failure: a meta-analysis and meta-regression. Exp Ther Med 6:929–936

    Article  PubMed  PubMed Central  Google Scholar 

  38. Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, Saliba F, Sauerbruch T, Klammt S, Ockenga J, Pares A, Wendon J, Brunnler T, Kramer L, Mathurin P, de la Mata M, Gasbarrini A, Mullhaupt B, Wilmer A, Laleman W, Eefsen M, Sen S, Zipprich A, Tenorio T, Pavesi M, Schmidt HH, Mitzner S, Williams R, Arroyo V (2013) Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 57:1153–1162

    Article  CAS  PubMed  Google Scholar 

  39. Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, Larsen FS, Gornbein J, Stange J, Blei AT (2007) Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 46:1853–1862

    Article  CAS  PubMed  Google Scholar 

  40. Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M, Klammt S, Loehr M, Liebe S, Mitzner S, Schmidt R, Stange J (2002) Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology 36:949–958

    CAS  PubMed  Google Scholar 

  41. 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 (2000) Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 6:277–286

    CAS  Google Scholar 

  42. Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, Sarrazin C, Hoste E, Van Vlierberghe H, Escorsell A, Hafer C, Schreiner O, Galle PR, Mancini E, Caraceni P, Karvellas CJ, Salmhofer H, Knotek M, Gines P, Kozik-Jaromin J, Rifai K (2012) Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 142(782–789):e783

    Google Scholar 

  43. Wong F, Raina N, Richardson R (2010) Molecular adsorbent recirculating system is ineffective in the management of type 1 hepatorenal syndrome in patients with cirrhosis with ascites who have failed vasoconstrictor treatment. Gut 59:381–386

    Article  CAS  PubMed  Google Scholar 

  44. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V (2013) Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144(1426–1437):1437.e1421–1429

    Google Scholar 

  45. European Association for the Study of the Liver (2017) EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67:145–172

    Article  Google Scholar 

  46. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M (2019) Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 69:394–419

    PubMed  Google Scholar 

  47. Bachs L, Parés A, Elena M, Piera C, Rodés J (1992) Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology 102:2077–2080

    Article  CAS  PubMed  Google Scholar 

  48. Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR (1997) Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology 113:1264–1269

    Article  CAS  PubMed  Google Scholar 

  49. Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ (2007) Sertraline as a first-line treatment for cholestatic pruritus. Hepatology 45:666–674

    Article  CAS  PubMed  Google Scholar 

  50. Reig A, Sesé P, Parés A (2018) Effects of bezafibrate on outcome and pruritus in primary biliary cholangitis with suboptimal ursodeoxycholic acid response. Am J Gastroenterol 113:49–55

    Article  CAS  PubMed  Google Scholar 

  51. Hegade VS, Kendrick SF, Dobbins RL, Miller SR, Thompson D, Richards D, Storey J, Dukes GE, Corrigan M, Oude Elferink RP, Beuers U, Hirschfield GM, Jones DE (2017) Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Lancet 389:1114–1123

    Article  CAS  PubMed  Google Scholar 

  52. Kremer AE, Oude Elferink RP, Beuers U (2011) Pathophysiology and current management of pruritus in liver disease. Clin Res Hepatol Gastroenterol 35:89–97

    Article  CAS  PubMed  Google Scholar 

  53. Parés A, Herrera M, Avilés J, Sanz M, Mas A (2010) Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers. J Hepatol 53:307–312

    Article  PubMed  CAS  Google Scholar 

  54. Leckie P, Tritto G, Mookerjee R, Davies N, Jones D, Jalan R (2012) ‘Out-patient’ albumin dialysis for cholestatic patients with intractable pruritus. Aliment Pharmacol Ther 35:696–704

    Article  CAS  PubMed  Google Scholar 

  55. Macia M, Avilés J, Navarro J, Morales S, García J (2003) Efficacy of molecular adsorbent recirculating system for the treatment of intractable pruritus in cholestasis. Am J Med 114:62–64

    Article  CAS  PubMed  Google Scholar 

  56. Parés A, Cisneros L, Salmerón JM, Caballería L, Mas A, Torras A, Rodés J (2004) Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol 99:1105–1110

    Article  PubMed  Google Scholar 

  57. Bellmann R, Graziadei IW, Feistritzer C, Schwaighofer H, Stellaard F, Sturm E, Wiedermann CJ, Joannidis M (2004) Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 10:107–114

    Google Scholar 

  58. Lemoine M, Revaux A, Francoz C, Ducarme G, Brechignac S, Jacquemin E, Uzan M, Ganne-Carrie N (2008) Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus. World J Gastroenterol 14:6572–6574

    Article  PubMed  PubMed Central  Google Scholar 

  59. Javouhey E, Ranchin B, Lachaux A, Boillot O, Martin X, Floret D, Cochat P (2009) Long-lasting extracorporeal albumin dialysis in a child with end-stage renal disease and severe cholestasis. Pediatr Transplant 13:235–239

    Article  PubMed  Google Scholar 

  60. Schaefer B, Schaefer F, Wittmer D, Engelmann G, Wenning D, Schmitt CP (2012) Molecular Adsorbents Recirculating System dialysis in children with cholestatic pruritus. Pediatr Nephrol 27:829–834

    Article  PubMed  Google Scholar 

  61. Horvatits T, Drolz A, Trauner M, Fuhrmann V (2019) Liver injury and failure in critical illness. Hepatology 70:2204–2215

    Article  PubMed  Google Scholar 

  62. Drolz A, Horvatits T, Roedl K, Rutter K, Staufer K, Haider DG, Zauner C, Heinz G, Schellongowski P, Kluge S, Trauner M, Fuhrmann V (2016) Outcome and features of acute kidney injury complicating hypoxic hepatitis at the medical intensive care unit. Ann Intensive Care 6:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Drolz A, Saxa R, Scherzer T, Fuhrmann V (2011) Extracorporeal artificial liver support in hypoxic liver injury. Liver Int Off J Int Assoc Study Liver 31(Suppl 3):19–23

    Article  Google Scholar 

  64. El Banayosy A, Kizner L, Schueler V, Bergmeier S, Cobaugh D, Koerfer R (2004) First use of the Molecular Adsorbent Recirculating System technique on patients with hypoxic liver failure after cardiogenic shock. ASAIO J 50:332–337

    Article  PubMed  CAS  Google Scholar 

  65. Fuhrmann V, Herkner H, Roedl K, Drolz A, Horvatits T, Horvatits K, Jarczak D, Zauner C, Schellongowski P, Heinz G, Trauner M, Kluge S (2019) Behandlung von sekundärem Leberversagen mit dem MARS®-System - eine randomisiert-kontrollierte Studie. In: Editor (ed)^(eds) Book Behandlung von sekundärem Leberversagen mit dem MARS®-System - eine randomisiert-kontrollierte Studie. City, pp 11–12

  66. van Mierlo KM, Schaap FG, Dejong CH, Olde Damink SW (2016) Liver resection for cancer: new developments in prediction, prevention and management of postresectional liver failure. J Hepatol 65:1217–1231

    Article  PubMed  Google Scholar 

  67. Catalina MV, Barrio J, Anaya F, Salcedo M, Rincon D, Clemente G, Banares R (2003) Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure. Liver Int Off J Int Assoc Study Liver 23(Suppl 3):39–43

    Article  CAS  Google Scholar 

  68. Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R (2005) Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol 43:142–148

  69. Stadlbauer V, Krisper P, Aigner R, Haditsch B, Jung A, Lackner C, Stauber RE (2006) Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure. Crit Care 10:R169

    Article  PubMed  PubMed Central  Google Scholar 

  70. Gilg (2016) Albumin dialysis with mars in post-hepatectomy liver failure (PHLF): experiences from two HPB centers. Surg Curr Res 6: 252:1–6

  71. Gilg S, Sparrelid E, Saraste L, Nowak G, Wahlin S, Strömberg C, Lundell L, Isaksson B (2018) The molecular adsorbent recirculating system in posthepatectomy liver failure: results from a prospective phase I study. Hepatol Commun 2:445–454

    Article  PubMed  PubMed Central  Google Scholar 

  72. Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, Durand F (2005) The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg 242:824–828

    Article  PubMed  PubMed Central  Google Scholar 

  73. Sparrelid E, Gilg S, van Gulik TM (2020) Systematic review of MARS treatment in post-hepatectomy liver failure. HPB (Oxf) 22:950–960

    Article  Google Scholar 

  74. Beyls C, Malaquin S, Huette P, Mary A, Besserve P, Roger PA, Bernasinski M, Guilbart M, Abou-Arab O, Dupont H, Mahjoub Y (2021) Hemodynamic impact of molecular adsorbent recirculating system in refractory vasoplegic shock due to calcium channel blocker poisoning. Int J Artif Organs 44(12):944–951

  75. Pichon N, Dugard A, Clavel M, Amiel JB, François B, Vignon P (2012) Extracorporeal albumin dialysis in three cases of acute calcium channel blocker poisoning with life-threatening refractory cardiogenic shock. Ann Emerg Med 59:540–544

    Article  PubMed  Google Scholar 

  76. Hassoun J, Hammer N, Magini G, Ponte B, Ongaro M, Rougemont AL, Goossens N, Frossard JL, Spahr L (2021) Management of acute Wilsonian hepatitis with severe hemolysis: a successful combination of chelation and MARS dialysis. Case Rep Hepatol 2021:5583654

    Google Scholar 

  77. Faybik P, Hetz H, Baker A, Bittermann C, Berlakovich G, Werba A, Krenn CG, Steltzer H (2003) Extracorporeal albumin dialysis in patients with Amanita phalloides poisoning. Liver Int Off J Int Assoc Study Liver 23(Suppl 3):28–33

    Article  CAS  Google Scholar 

  78. De Bruyn T, Meijers B, Evenepoel P, Laub R, Willems L, Augustijns P, Annaert P (2012) Stability of therapeutic albumin solutions used for molecular adsorbent recirculating system-based liver dialysis. Artif Organs 36:29–41

    Article  PubMed  CAS  Google Scholar 

  79. Krisper P, Tiran B, Fliser D, Haditsch B, Stadlbauer V, Otto R, Ernst T, Kretschmer U, Stauber RE, Haller H, Holzer H, Manns MP, Rifai K (2010) Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus. Artif Organs 34:84–88

    Article  CAS  PubMed  Google Scholar 

  80. Tan HK, Yang WS, Chow P, Lui HF, Choong HL, Wong KS (2007) Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system. Artif Organs 31:193–199

    Article  PubMed  Google Scholar 

  81. Faybik P, Hetz H, Mitterer G, Krenn CG, Schiefer J, Funk GC, Bacher A (2011) Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system. Crit Care Med 39:273–279

    Article  CAS  PubMed  Google Scholar 

  82. Meijers B, Laleman W, Vermeersch P, Nevens F, Wilmer A, Evenepoel P (2012) A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System. Crit Care (Lond, Engl) 16:R20

    Article  Google Scholar 

  83. Tan HK (2004) Molecular adsorbent recirculating system (MARS). Ann Acad Med Singap 33:329–335

    CAS  PubMed  Google Scholar 

  84. Sponholz C, Matthes K, Rupp D, Backaus W, Klammt S, Karailieva D, Bauschke A, Settmacher U, Kohl M, Clemens MG, Mitzner S, Bauer M, Kortgen A (2016) Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure—a prospective, randomised crossover study. Crit Care (Lond, Engl) 20:2

    Article  Google Scholar 

  85. Dyla A, Mielnicki W, Bartczak J, Zawada T, Garba P (2017) Effectiveness and safety assessment of citrate anticoagulation during albumin dialysis in comparison to other methods of anticoagulation. Artif Organs 41:818–826

    Article  CAS  PubMed  Google Scholar 

  86. Thai C, Oben C, Wagener G (2020) Coagulation, hemostasis, and transfusion during liver transplantation. Best Pract Res Clin Anaesthesiol 34:79–87

    Article  PubMed  Google Scholar 

  87. Evenepoel P, Laleman W, Wilmer A, Claes K, Kuypers D, Bammens B, Nevens F, Vanrenterghem Y (2006) Prometheus versus molecular adsorbents recirculating system: comparison of efficiency in two different liver detoxification devices. Artif Organs 30:276–284

    Article  CAS  PubMed  Google Scholar 

  88. Schneider AG, Journois D, Rimmelé T (2017) Complications of regional citrate anticoagulation: accumulation or overload? Crit Care (Lond, Engl) 21:281

    Article  Google Scholar 

  89. Weiler S, Vogelsinger H, Joannidis M, Dunzendorfer S, Bellmann R (2011) Influence of albumin dialysis on pharmacokinetics of amphotericin B colloidal dispersion and amphotericin B lipid complex. Artif Organs 35:667–671

    Article  CAS  PubMed  Google Scholar 

  90. Aguilar G, Azanza JR, Sádaba B, Badenes R, Ferrando C, Delgado C, Hernández J, Parra MA, Puig J, Carbonell JA, Navarro D, Belda FJ (2014) Pharmacokinetics of anidulafungin during albumin dialysis. Crit Care (Lond, Engl) 18:422

    Article  Google Scholar 

  91. Personett HA, Larson SL, Frazee EN, Nyberg SL, El-Zoghby ZM (2015) Extracorporeal elimination of piperacillin/tazobactam during molecular adsorbent recirculating system therapy. Pharmacotherapy 35:e136-139

    Article  CAS  PubMed  Google Scholar 

  92. Ruggero MA, Argento AC, Heavner MS, Topal JE (2013) Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure. Transpl Infect Dis Off J Transplant Soc 15:214–218

    Article  CAS  Google Scholar 

  93. Personett HA, Larson SL, Frazee EN, Nyberg SL, Leung N, El-Zoghby ZM (2014) Impact of molecular adsorbent recirculating system therapy on tacrolimus elimination: a case report. Transplant Proc 46:2440–2442

    Article  CAS  PubMed  Google Scholar 

  94. Falkensteiner C, Kortgen A, Leonhardt J, Bauer M, Sponholz C (2021) Comparison of albumin dialysis devices molecular adsorbent recirculating system and ADVanced Organ Support system in critically ill patients with liver failure—a retrospective analysis. Ther Apher Dial Off Peer-Rev J Int Soc Apher Jpn Soc Apher Jpn Soc Dial Ther 25:225–236

    CAS  Google Scholar 

  95. Fuhrmann V, Weber T, Roedl K, Motaabbed J, Tariparast A, Jarczak D, de Garibay APR, Kluwe J, Boenisch O, Herkner H, Kellum JA, Kluge S (2020) Advanced organ support (ADVOS) in the critically ill: first clinical experience in patients with multiple organ failure. Ann Intensive Care 10:96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Tan EX, Wang MX, Pang J, Lee GH (2020) Plasma exchange in patients with acute and acute-on-chronic liver failure: a systematic review. World J Gastroenterol 26:219–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Schmidt LE, Wang LP, Hansen BA, Larsen FS (2003) Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 9:290–297

    Google Scholar 

  98. Novelli G, Rossi M, Pretagostini M, Pugliese F, Ruberto F, Novelli L, Nudo F, Bussotti A, Corradini S, Martelli S, Berloco PB (2005) One hundred sixteen cases of acute liver failure treated with MARS. Transplant Proc 37:2557–2559

    Article  CAS  PubMed  Google Scholar 

  99. El Banayosy A, Cobaugh D, Pauly A, Kizner L, Korfer R (2007) Albumindialyse bei patienten mit sekundärem leberversagen nach kariogenem schock. Intensivemed 44:149–157

    Article  Google Scholar 

  100. 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 (2017) Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure—a retrospective analysis. Crit Care Med 45:1616–1624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are grateful to Bruno Trumbic, MD (Paris, France) for assistance in assembling the manuscript. A special dedication to Roger Williams CBE, for his great devotion to liver research and his contribution and inspiration to the development of devices for liver support therapy.

Funding

The study was part of an Investigator-Initiated Research (IIR) Grant Program from Baxter International Inc. Baxter® was not involved in the conception of the study, the expert’s selection and drafting of the manuscript.

Author information

Authors and Affiliations

  1. AP-HP Hôpital Paul Brousse, Hepato-Biliary Center and Liver Transplant ICU, University Paris Saclay, INSERM Unit N°1193, Villejuif, France

    Faouzi Saliba & Didier Samuel

  2. Gastroenterology and Hepatology Department, Hospital General Universitario Gregorio Marañón, IISGM, Madrid, Spain

    Rafael Bañares

  3. Facultad de Medicina, Universidad Complutense, Madrid, Spain

    Rafael Bañares

  4. CIBERehd, Madrid, Spain

    Rafael Bañares

  5. Department of Hepatology and Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Fin Stolze Larsen

  6. Medical Intensive Care Unit, Department of General Internal Medicine, KU Leuven University Hospitals Leuven, Leuven, Belgium

    Alexander Wilmer

  7. Liver Unit, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain

    Albert Parés

  8. Division of Nephrology and Fraunhofer Institute for Cell Therapy and Immunology, Department of Medicine, University Hospital Rostock, Rostock, Germany

    Steffen Mitzner

  9. Center for Extracorporeal Organ Support, Nephrology, Internal Medicine, Rostock University Medical Center, Rostock, Germany

    Jan Stange

  10. Albutec GmbH, Rostock, Germany

    Jan Stange

  11. Klinik für Innere Medizin, Heilig Geist-Krankenhaus, Cologne, Germany

    Valentin Fuhrmann

  12. Klinik für Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    Valentin Fuhrmann

  13. Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Solna, Sweden

    Stefan Gilg

  14. Department of HPB Surgery, Karolinska University Hospital, Stockholm, Sweden

    Stefan Gilg

  15. Southern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA, 92118, USA

    Tarek Hassanein

  16. NORER 96 SL, Barcelona, Spain

    Josep Torner

  17. Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, PhyMedExp, INSERM U1046, CNRS UMR, 9214, Montpellier Cedex 5, France

    Samir Jaber

  18. Département d’Anesthésie Réanimation B (DAR B), 80 Avenue Augustin Fliche, 34295, Montpellier, France

    Samir Jaber

Authors
  1. Faouzi Saliba
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  2. Rafael Bañares
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  3. Fin Stolze Larsen
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  4. Alexander Wilmer
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  5. Albert Parés
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  6. Steffen Mitzner
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  7. Jan Stange
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  8. Valentin Fuhrmann
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  9. Stefan Gilg
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  10. Tarek Hassanein
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  11. Didier Samuel
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  12. Josep Torner
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  13. Samir Jaber
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Contributions

FS, SJ and JT appointed the expert panel, organized the meetings and coordinated the panel group, drafted and wrote the final version of the manuscript. All authors participated individually to the draft writing, the consensus and approved the statements and final version of the manuscript.

Corresponding author

Correspondence to Samir Jaber.

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Conflicts of interest

FS has received speaker’s honoraria and/or research grants from Novartis, Astellas, Chiesi, Gilead, Merck Sharp and Dohme, Neovie, Biotest and Baxter. RB has received speaker’s honoraria and/or research grants from Gilead, abbvie, Janssen, Gore Baxter. FL has nothing to declare. AW has no conflict of interest. AP has received grant funding, personal fees, and advisory board fees from Intercept Pharmaceuticals and Genfit; advisory board fees and fees for teaching from Novartis; and personal fees from CymaBay Therapeutics and Inova Diagnostics. SM has received speaker`s honoraria and/or research grants from Amgen, Astellas, Baxter, BMS/Pfizer, CytoSorbents, Pentracor, Vifor. JS is chairman of the board of Albutec GmbH. VF declare presentations for Fresenius, Baxter, ADVITOS, CSL-Behring, Merz, Advisory board. SG declare no conflict of interest. TH is consultant for DIALIVE. On advisory committee and received consultancy from AbbVie, Bristol-Myers Squibb, Gilead, Malinckrodt, Merck, and Organovo. Received research grants from AbbVie, Allergan, Amarex/Cytodyn, Astra Zeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta, Galectin, Gilead, Grifols, Intercept, Merck, Mirum, Novartis, Novo Nordisk, Pfizer, Salix Pharmaceuticals, Sonic Incytes, and Terns Pharmaceuticals. DS received research grants Astellas and honoraria from Goliver and Biotest. JT, declare no conflict of interest. JT declares no conflict of interest. SJ declares consulting fees from Drager, Fresenius-Xenios, Medtronic, Mindray and Fisher & Paykel.

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134_2022_6802_MOESM1_ESM.pdf

Supplemental figure 1. Molecular structure of human serum albumin and binding sites (adapted from Bernardi M. et al [9]). (PDF 2047 kb)

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Saliba, F., Bañares, R., Larsen, F.S. et al. Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts. Intensive Care Med 48, 1352–1367 (2022). https://doi.org/10.1007/s00134-022-06802-1

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