Skip to main content
Log in

A comparison among three different apheretic techniques for treatment of hyperbilirubinemia

  • Original Article
  • Artificial Liver, Pancreas
  • Published:
Journal of Artificial Organs Aims and scope Submit manuscript

Abstract

Liver failure is associated to high mortality due to the accumulation of protein-bound metabolites, such as bilirubin, not removed by conventional hemodialysis. Different methods can efficiently remove them, such as the molecular adsorbent recirculating system (MARS), plasma exchange (PEX), and bilirubin or plasma adsorption perfusion (PAP). No direct comparison exists between MARS, PEX and PAP, and current guidelines do not specify which method (and when) to use. We have retrospectively evaluated MARS, PEX and PAP in their effectiveness in lowering plasma bilirubin concentration, and their effects on liver and kidney function. A total of 98 patients have been recruited, which comprised 68 patients treated with PAP (177 sessions), 16 patients with PEX (41 sessions) and 11 patients with MARS (21 sessions). Bilirubin, creatinine, liver enzymes were analyzed before and after the first treatment with each technique. The three methods did not differ for bilirubin lowering efficiency, with MARS showing only slightly less effective reductions. Finally, the three techniques did not differ in the amount of change of cholinesterase, but a lower reduction in AST was found using PAP. Our retrospective observation is one of the largest case series of hepatic failure treated with bilirubin absorption. The choice of the technique cannot be based on the desired reduction in bilirubin concentration. Based on costs and duration of treatment, we suggest that PAP could be considered as a first-line approach. In case of kidney involvement, MARS remains a valuable option.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hansen TW. Bilirubin brain toxicity. J Perinatol. 2001;21:S48–51.

    Article  Google Scholar 

  2. Bach DR, Kindler J, Strik WK. Elevated bilirubin in acute and transient psychotic disorder. Pharmacopsychiatry. 2010;43:12–6. doi:10.1055/s-0029-1237376 (Epub 2009 Dec 10).

  3. Rafat C, Burbach M, Brochériou I, Zafrani L, Callard P, Rondeau E, Hertig A. Bilirubin-associated acute tubular necrosis in a kidney transplant recipient. Am J Kidney Dis. 2013;61:782–5.

    Article  CAS  PubMed  Google Scholar 

  4. Takeda Y, Takeda Y, Tomimoto S, Tani T, Narita H, Kimura G. Bilirubin as a prognostic marker in patients with pulmonary arterial hypertension. BMC Pulm Med. 2010;10:22. doi:10.1186/1471-2466-10-22.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Uslu A, Cayci M, Nart A, Karaca C, Zalluhoglu N, Gürkan A, Varilsuha C, Adagülü H. Renal failure in obstructive jaundice. Hepatogastroenterology. 2005;52:52–4.

    CAS  PubMed  Google Scholar 

  6. Patzer J. Principles of bound solute dialysis. Ther Apher Dial. 2006;10:118–24.

    Article  PubMed  Google Scholar 

  7. Mandal AK, King KE, Humphreys SL, Maley WR, Burdick JF, Klein AS. Plasmapheresis: an effective therapy for primary allograft nonfunction after liver transplantation. Transplantation 2000;70:216–20.

    Google Scholar 

  8. Stange 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;17:809–13.

    Google Scholar 

  9. Rifai K, Ernst T, Kretschmer U, Bahr MJ, Schneider A, Hafer C, Haller H, Manns MP, Fliser D. Prometheus—a new extracorporeal system for the treatment of liver failure. J Hepatol. 2003;39:984–90.

    Article  Google Scholar 

  10. Ott R, Rupprecht H, Born G, Müller V, Reck T, Hohenberger W, Köckerling F. Plasma separation and bilirubin adsorption after complicated liver transplantation: a therapeutic approach to excessive hyperbilirubinemia. Transplantation 1998;65:434–7

    Article  CAS  PubMed  Google Scholar 

  11. Adani GL, Lorenzin D, Currò G, Sainz-Barriga M, Comuzzi C, Bresadola V, Avellini C, Baccarani U. Selective bilirubin removal by plasma treatment with Plasorba BR-350 for early cholestatic graft dysfunction. Transplant Proc. 2007;39:1904–6.

    Article  CAS  PubMed  Google Scholar 

  12. Senf R, Klingel R, Kurz S, Tullius S, Sauer I, Frei U, Schindler R. Bilirubin-adsorption in 23 critically ill patients with liver failure. Int J Artif Organs. 2004;27:717–22.

    Article  Google Scholar 

  13. Mitzner SR, Jan Stange J, Klammt S, Peszynski P, Schmidt R, Nöldge-Schomburg G. Extra-corporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. J Am Soc Nephrol. 2001;12:S75–82.

    Google Scholar 

  14. Davenport A. Extracorporeal support for patients with hepatic failure. Hemodial Int. 2003;7:256–63.

    Google Scholar 

  15. Khuroo MS, Khuroo MS, Farahat KL. Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis. Liver Transplant. 2004;10:1099–106.

    Article  Google Scholar 

  16. Novelli G, Rossi M, Ferretti G, Pugliese F, Ruberto F, Lai Q, Novelli S, Piemonte V, Turchetti L, Morabito V, Annesini MC, Berloco PB. Predictive criteria for the outcome of patients with acute liver failure treated with the albumin dialysis molecular adsorbent recirculating system. Ther Apher Dial. 2009;13:404–12.

    Article  Google Scholar 

  17. Coşkun R, Uslup S, Gündoğan K, Pala C, Akbudak IH, Sungur M, Güven M. The Effectiveness of bilirubin column on severe hyperbilirubinemia in a patient with cardiac cirrhosis. Erciyes Med J. 2014;36:82–4.

    Google Scholar 

  18. 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, RELIEF study group. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57:1153–62.

    Article  PubMed  Google Scholar 

  19. Szczepiorkowski ZM, Shaz BH, Bandarenko N, Winters JL. The new approach to assignment of ASFA categories introduction to the fourth special issue: clinical applications of therapeutic apheresis. J Clin Apher. 2007;22:96–105.

    Article  PubMed  Google Scholar 

  20. LópezVelázquez JA, Chávez-Tapia NC, Ponciano-Rodríguez G, Sánchez-Valle V, Caldwell SH, Uribe M, Méndez-Sánchez N. Bilirubin alone as a biomarker for short-term mortality in acute-on-chronic liver failure: an important prognostic indicator. Ann Hepatol. 2014;13:98–104.

    Google Scholar 

  21. Chamuleau RA, Aronson DC, Frederiks WM, Bosman DK, Smit JJ, Maas MA, Jansen PL. Liver regeneration after partial hepatectomy in rats with defective bilirubin conjugation or biliary excretion. Dig Dis Sci. 1991;36:510–2.

    Article  CAS  PubMed  Google Scholar 

  22. Hassanein TI, Schade RR, Hepburn IS. Acute-on-chronic liver failure: extracorporeal liver assist devices. Curr Opin Crit Care. 2011;17:195–203.

    Article  PubMed  Google Scholar 

  23. Lee JY, Kim SB, Chang JW, Park SK, Kwon SW, Song KW, Hwang S, Lee SG. Comparison of the molecular adsorbent recirculating system and plasmapheresis for patients with graft dysfunction after liver transplantation. Transplant Proc. 2010;42:2625–30.

    Article  CAS  PubMed  Google Scholar 

  24. Schaefer B, Schaefer F, Engelmann G, Meyburg J, Heckert KH, Zorn M, Schmitt CP. Comparison of molecular adsorbents recirculating system (MARS) dialysis with combined plasma exchange and haemodialysis in children with acute liver failure. Nephrol Dial Transplant. 2011;26:3633–9.

    Article  CAS  PubMed  Google Scholar 

  25. 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. Crit Care. 2006;10:R108.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Dethloff T, Tofteng F, Frederiksen HJ, Hojskov M, Hansen BA, Larsen FS. Effect of Prometheus liver assist system on systemic hemodynamics in patients with cirrhosis: a randomized controlled study. World J Gastroenterol. 2008;14:2065–71.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Krisper P, Haditsch B, Stauber R, Jung A, Stadlbauer V, Trauner M, Holzer H, Schneditz D. In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation. J Hepatol. 2005;43:451–7.

    Article  CAS  PubMed  Google Scholar 

  28. Gong D, Cruz D, Ronco C. Depurative capacity of molecular adsorbent recycling system (MARS): a focus on bilirubin removal. Int J Artif Organs. 2008;31:875–81.

    Article  CAS  PubMed  Google Scholar 

  29. Gong D, Ji D, Ren B, Tao J, Xu B, Ronco C, Li L. Significant decrease in dialysate albumin concentration during molecular adsorbent recirculating system (M.A.R.S.) therapy. Int J Artif Organs. 2008;31:333–9.

    Article  CAS  PubMed  Google Scholar 

  30. Steiner C, Sen S, Stange J, Williams R, Jalan R. Binding of bilirubin and bromo-sulphthalein to albumin: implications for understanding the pathophysiology of liver failure and its management. Liver Transpl. 2004;10:1531–8.

    Article  PubMed  Google Scholar 

  31. Rozga J, Malkowski P. Artificial liver support: quo vadis? Ann Transplant. 2010;15:92–101.

    PubMed  Google Scholar 

  32. Nakae H, Eguchi Y, Saotome T, Yoshioka T, Yoshimura N, Kishi Y, Naka T, Furuya T. Multicenter study of plasma diafiltration in patients with acute liver failure. Ther Apher Dial 2010;14:444–50.

    Article  Google Scholar 

  33. Santoro A, Mancini E, Ferramosca E, Faenza S. Liver support systems. In: Ronco C, Bellomo R, Kellum JA, editors. Acute kidney injury. Contrib Nephrol. Basel, Karger, 2007. Vol. 156, p. 396–404.

  34. Rademacher S, Oppert M, Jörres A. Artificial extracorporeal liver support therapy in patients with severe liver failure. Expert Rev Gastroenterol Hepatol. 2011;5:591–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. Alfonso Ramunni for critical reading and suggestions.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Davide Viggiano or Corrado Pluvio.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Davide Viggiano, Emanuela de Pascale and Gaia Marinelli should be considered as equal contributors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Viggiano, D., de Pascale, E., Marinelli, G. et al. A comparison among three different apheretic techniques for treatment of hyperbilirubinemia. J Artif Organs 21, 110–116 (2018). https://doi.org/10.1007/s10047-017-0986-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10047-017-0986-1

Keywords

Navigation