First clinical experience in 14 patients treated with ADVOS: a study on feasibility, safety and efficacy of a new type of albumin dialysis

Wolfgang Huber, Benedikt Henschel, Roland Schmid, Ahmed Al-Chalabi, Wolfgang Huber, Benedikt Henschel, Roland Schmid, Ahmed Al-Chalabi

Abstract

Background: Liver failure (LF) is associated with prolonged hospital stay, increased cost and substantial mortality. Due to the limited number of donor organs, extracorporeal liver support is suggested as an appealing concept to "bridge to transplant" or to avoid transplant in case of recovery. ADVanced Organ Support (ADVOS) is a new type of albumin dialysis, that provides rapid regeneration of toxin-binding albumin by two purification circuits altering the binding capacities of albumin by biochemical (changing of pH) and physical (changing of temperature) modulation of the dialysate. It was the aim of this study to evaluate feasibility, efficacy and safety of ADVOS in the first 14 patients ever treated with this procedure.

Methods: Patients included suffered from acute on chronic LF (n = 9) or "secondary" LF (n = 5) which resulted from non-hepatic diseases such as sepsis. The primary endpoint was the change of serum bilirubin, creatinine and serum BUN levels before and after the first treatment with ADVOS. The Wilcoxon Signed Rank test for paired samples was used to analyze the data.

Results: A total of 239 treatments (1 up to 101 per patient) were performed in 14 patients (6 female, 8 male). Mean age 54 ± 13; MELD-score 34 ± 7; CLIF-SOFA 15 ± 3. Serum bilirubin levels were significantly decreased by 32% during the first session (26.0 ± 15.4 vs. 17.7 ± 10.5 mg/dl; p = 0.001). Similarly, serum creatinine (2.2 ± 0.8 vs. 1.6 ± 0.7 mg/dl; p = 0.005) and serum BUN (49.4 ± 23.3 vs. 31.1 ± 19.7 mg/dl; p = 0.003), were significantly lowered by 27% and 37%, respectively. None of the treatment sessions had to be interrupted due to side effects related to the procedure.

Conclusion: ADVOS efficiently eliminates water- and protein-bound toxins in humans with LF. ADVOS is feasible in patients with advanced LF which is emphasized by a total number of more than 100 treatment sessions in one single patient.

Keywords: Acute liver failure; Acute-on-chronic-liver failure; CLIF-SOFA; Chronic liver failure; Extracorporeal liver support; Fractionated plasma separation and adsorption; Liver transplantation; MELD; Molecular Adsorbent Recirculating System; Single pass albumin dialysis.

Figures

Fig. 1
Fig. 1
The advanced organ support (ADVOS) device
Fig. 2
Fig. 2
Boxplots depicting the time course of serum bilirubin
Fig. 3
Fig. 3
Boxplots depicting the time course of serum creatinine
Fig. 4
Fig. 4
Boxplots depicting the time course of serum BUN

References

    1. Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, et al. Acute-on chronic liver failure. J Hepatol. 2012;57(6):1336–48. doi: 10.1016/j.jhep.2012.06.026.
    1. Moreau R, Arroyo V. Acute-on-chronic liver failure: a new clinical entity. Clin Gastroenterol Hepatol. 2015;13(5):836–41. doi: 10.1016/j.cgh.2014.02.027.
    1. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37. doi: 10.1053/j.gastro.2013.02.042.
    1. Kramer L, Jordan B, Druml W, Bauer P, Metnitz PG. Incidence and prognosis of early hepatic dysfunction in critically ill patients--a prospective multicenter study. Crit Care Med. 2007;35(4):1099–104. doi: 10.1097/01.CCM.0000259462.97164.A0.
    1. Lee M, Lee JH, Oh S, Jang Y, Lee W, Lee HJ, et al. CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis. Liver Int. 2015;35(1):46–57. doi: 10.1111/liv.12683.
    1. 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 Hepatol. 1999;31(6):1080–5. doi: 10.1016/S0168-8278(99)80322-5.
    1. Sponholz C, Matthes K, Rupp D, Backaus W, Klammt S, Karailieva D, et al. Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure - a prospective, randomised crossover study. Crit Care. 2016;20(1):2. doi: 10.1186/s13054-015-1159-3.
    1. Hassanein TI, Schade RR, Hepburn IS. Acute-on-chronic liver failure: extracorporeal liver assist devices. Curr Opin Crit Care. 2011;17(2):195–203. doi: 10.1097/MCC.0b013e328344b3aa.
    1. Laleman W, Wilmer A, Evenepoel P, Elst IV, Zeegers M, Zaman Z, 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(4):R108. doi: 10.1186/cc4985.
    1. Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57(3):1153–62. doi: 10.1002/hep.26185.
    1. Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M, et al. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology. 2002;36(4 Pt 1):949–58. doi: 10.1053/jhep.2002.36130.
    1. Kortgen A, Rauchfuss F, Gotz 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(5):419–25. doi: 10.1111/j.1744-9987.2009.00760.x.
    1. Sen S, Davies NA, Mookerjee RP, Cheshire LM, Hodges SJ, Williams R, et al. Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl. 2004;10(9):1109–19. doi: 10.1002/lt.20236.
    1. Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, 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(8):522–31. doi: 10.7326/0003-4819-159-8-201310150-00005.
    1. 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 Transpl. 2003;9(3):290–7. doi: 10.1053/jlts.2003.50051.
    1. Hessel FP, Bramlage P, Wasem J, Mitzner SR. Cost-effectiveness of the artificial liver support system MARS in patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol. 2010;22(2):213–20. doi: 10.1097/MEG.0b013e3283314e48.
    1. Qin G, Shao JG, Wang B, Shen Y, Zheng J, Liu XJ, et al. Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience. Medicine. 2014;93(28):e338. doi: 10.1097/MD.0000000000000338.
    1. Xu X, Liu X, Ling Q, Wei Q, Liu Z, Zhou L, et al. Artificial liver support system combined with liver transplantation in the treatment of patients with acute-on-chronic liver failure. PLoS One. 2013;8(3):e58738. doi: 10.1371/journal.pone.0058738.
    1. Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology. 2012;142(4):782–9. doi: 10.1053/j.gastro.2011.12.056.
    1. Figaro S, Pereira U, Rada H, Semenzato N, Pouchoulin D, Legallais C. Development and validation of a bioartificial liver device with fluidized bed bioreactors hosting alginate-encapsulated hepatocyte spheroids. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:1335–8.
    1. Nastos C, Kalimeris K, Papoutsidakis N, Defterevos G, Pafiti A, Kalogeropoulou E, et al. Bioartificial liver attenuates intestinal mucosa injury and gut barrier dysfunction after major hepatectomy: Study in a porcine model. Surgery. 2016. Epub 2016/02/06.
    1. Hassanein TI, Tofteng F, Brown RS, Jr, McGuire B, Lynch P, Mehta R, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology. 2007;46(6):1853–62. doi: 10.1002/hep.21930.
    1. Seige M, Kreymann B, Jeschke B, Schweigart U, Kopp KF, Classen M. Long-term treatment of patients with acute exacerbation of chronic liver failure by albumin dialysis. Transplant Proc. 1999;31(1–2):1371–5. doi: 10.1016/S0041-1345(98)02033-8.
    1. Al-Chalabi A, Matevossian E, AK VT, Luppa P, Neiss A, Schuster T, et al. Evaluation of the Hepa Wash(R) treatment in pigs with acute liver failure. BMC Gastroenterol. 2013;13:83. doi: 10.1186/1471-230X-13-83.
    1. Arroyo V, Moreau R, Jalan R, Gines P. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatol. 2015;62(1 Suppl):S131–43. doi: 10.1016/j.jhep.2014.11.045.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10. doi: 10.1007/BF01709751.
    1. Wiesner RH, McDiarmid SV, Kamath PS, Edwards EB, Malinchoc M, Kremers WK, et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl. 2001;7(7):567–80. doi: 10.1053/jlts.2001.25879.
    1. Mitzner SR. Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) Ann Hepatol. 2011;10(Suppl 1):S21–8.

Source: PubMed

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