Skip to main content
SpringerLink
Log in

Clinical application of bioartificial liver support systems

  • Chapter
Encephalopathy and Nitrogen Metabolism in Liver Failure

Abstract

Mortality of acute liver failure (ALF) is high despite maximal supportive intensive care. Mortality ranges from 60 to 90% depending on the cause of liver disease. Survival of patients with ALF caused by acute hepatitis B is 12–23% in Western Europe.1 Since the 1960’s several therapies to assist the failing liver have been introduced. These therapies range from drug treatment, to liver support devices and liver transplantation. At present, the best treatment for ALF is orthotopic liver transplantation (OLT). Emergency OLT is associated with a one-year survival of 60 to 90%, depending on the cause of ALF and selection criteria for OLT.1–4 Adam et al. 5 reported an overall one-year survival of 76% in 22,089 patients that underwent liver transplantation since 1988. The one-year survival in 2314 patients with ALF who underwent liver transplantation was 61%. However, due to the shortage of donor livers, a considerable number of patients with ALF die while on the waiting list for OLT. Despite improved liver transplantation techniques and efforts to increase the donor liver pool, such as split liver, living related donor liver and adjustments to donor legislation, the availability of donor livers is far less than the demand. In the USA in 2001, 17,500 patients were waiting for OLT. Of these, 5177 (30%) received a donor liver, and 1975 (11%) patients with fulminant hepatic failure due to a variety of different causes died while waiting for OLT.6

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bernuau J and Benhamou JP. Fulminant and subfulminant liver failure. In McIntyre N, Benhamou JP, Bircher J, Rizzetto M, Rodes J (Eds). Oxford Textbook of Clinical Hepatology. Oxford-New York-Tokyo: Oxford University Press; 1991: 923–942.

    Google Scholar 

  2. Lidofsky SD, Bass NM, Prager MC, Washington DE, Read AE, Wright TL, Ascher NL, Roberts JP, Scharschmidt BF and Lake JR. Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. Hepatology 1992; 16: 1–7.

    Article  PubMed  CAS  Google Scholar 

  3. de Rave S, Tilanus HW, van Der LJ, de Man RA, van Der BB, Hop WJ, IJzermans JM, Zondervan PE and Metselaar HJ. The importance of orthotopic liver transplantation in acute hepatic failure. Transpl Int 2002; 15: 29–33.

    Article  PubMed  Google Scholar 

  4. Wall WJ and Adams PC. Liver transplantation for fulminant hepatic failure: North American experience. Liver Transpl Surg 1995; 1: 178–182.

    Article  PubMed  CAS  Google Scholar 

  5. Adam R, Cailliez V, Majno P, Karam V, McMaster P, Caine RY, O’Grady J, Pichlmayr R, Neuhaus P, Otte JB, Hoeckerstedt K and Bismuth H. Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study. Lancet 2000; 356: 621–627.

    Article  PubMed  CAS  Google Scholar 

  6. United Network for Organ Sharing. Liver transplantation data 2002; www.unos.org. 2002. Ref Type: Internet Communication.

    Google Scholar 

  7. Stange J, Hassanein TI, Mehta R, Mitzner SR and 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 Organs 2002;26:103–110.

    Article  PubMed  Google Scholar 

  8. Ash SR. Extracorporeal blood detoxification by sorbents in treatment of hepatic encephalopathy. Adv Ren Replace Ther 2002; 9: 3–18.

    Article  PubMed  Google Scholar 

  9. Lanjuan L, Qian Y, Jianrong H, Xiaowei X, Yuemei C, Yagang C, Weihang M, Zhi C and Suzhen F. Severe hepatitis treated with an artificial liver support system. Int J Artif Organs 2001; 24: 297–303.

    PubMed  CAS  Google Scholar 

  10. Seige M, Kreymann B, Jeschke B, Schweigart U, Kopp KF and Classen M. Long-term treatment of patients with acute exacerbation of chronic liver failure by albumin dialysis. Transplant Proc 1999; 31: 1371–1375.

    Article  PubMed  CAS  Google Scholar 

  11. Matsumura KN, Guevara GR, Huston H, Hamilton WL, Rikimaru M, Yamasaki and Matsumura MS. Hybrid bioartiflcial liver in hepatic failure: preliminary clinical report. Surgery 1987; 101: 99–103.

    PubMed  CAS  Google Scholar 

  12. Margulis MS, Erukhimov EA, Andreiman LA and Viksna LM. Temporary organ substitution by hemoperfusion through suspension of active donor hepatocytes in a total complex of intensive therapy in patients with acute hepatic insufficiency. Resuscitation 1989; 18: 85–94.

    Article  PubMed  CAS  Google Scholar 

  13. Sussman NL and Kelly JH. Extracorporeal liver support: cell-based therapy for the failing liver. Am J Kidney Dis 1997; 30: S66–S71.

    Article  PubMed  CAS  Google Scholar 

  14. Ellis AJ, Hughes RD, Wendon JA, Dunne J, Langley PG, Kelly JH, Gislason GT, Sussman NL and Williams R. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology 1996; 24: 1446–1451.

    Article  PubMed  CAS  Google Scholar 

  15. Sussman NL, Gislason GT, Conlin CA and Kelly JH. The Hepatix extracorporeal liver assist device: initial clinical experience. Artif Organs 1994; 18: 390–396.

    Article  PubMed  CAS  Google Scholar 

  16. Sussman NL, Gislason GT and Kelly JH. Extracorporeal liver support. Application to fulminant hepatic failure. J Clin Gastroenterol 1994; 18: 320–324.

    Article  PubMed  CAS  Google Scholar 

  17. Gislason GT, Lobdell DD, Kelly JH and Sussman NL. A treatment system for implementing an extracorporeal liver assist device. Artif Organs 1994; 18: 385–389.

    Article  PubMed  CAS  Google Scholar 

  18. Sussman NL and Kelly JH. Improved liver function following treatment with an extracorporeal liver assist device. Artif Organs 1993; 17: 27–30.

    Article  PubMed  CAS  Google Scholar 

  19. Demetriou AA, Rozga J, Podesta L, Lepage E, Morsiani E, Moscioni AD, Hoffman A, McGrath M, Kong L and Rosen H. Early clinical experience with a hybrid bioartiflcial liver. Scand J Gastroenterol Suppl 1995; 208:111–117.

    Article  PubMed  CAS  Google Scholar 

  20. Rozga J, Holzman MD, Ro MS, Griffin DW, Neuzil DF, Giorgio T, Moscioni AD and Demetriou AA. Development of a hybrid bioartiflcial liver. Ann Surg 1993; 217: 502–509.

    Article  PubMed  CAS  Google Scholar 

  21. Samuel D, Ichai P, Feray C, Saliba F, Azoulay D, Arulnaden JL, Debat P, Gigou M, Adam R, Bismuth A, Castaing D and Bismuth H. Neurological improvement during bioartiflcial liver sessions in patients with acute liver failure awaiting transplantation. Transplantation 2002; 73: 257–264.

    Article  PubMed  CAS  Google Scholar 

  22. Hui T, Rozga J and Demetriou AA. Bioartiflcial liver support. J Hepatobiliary Pancreat Surg 2001; 8:1–15.

    Article  PubMed  CAS  Google Scholar 

  23. Watanabe FD, Mullon CJ, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi, Khalili T, Arnaout W, Shackleton CR, Rozga J, Solomon B and Demetriou AA. Clinical experience with a bioartiflcial liver in the treatment of severe liver failure. A phase I clinical trial. Ann Surg 1997; 225: 484–491.

    Article  PubMed  CAS  Google Scholar 

  24. Chen SC, Hewitt WR, Watanabe FD, Eguchi S, Kahaku E, Middleton Y, Rozga J and Demetriou AA. Clinical experience with a porcine hepatocyte-based liver support system. Int J Artif Organs 1996; 19: 664–669.

    PubMed  CAS  Google Scholar 

  25. Demetriou AA, Watanabe F and Rozga J. Artificial hepatic support systems. Prog Liver Dis 1995; 13:331–348.

    PubMed  CAS  Google Scholar 

  26. Arkadopoulos N, Detry O, Rozga J and Demetriou AA. Liver assist systems: state of the art. Int J Artif Organs 1998; 21: 781–787.

    PubMed  CAS  Google Scholar 

  27. Neuzil DF, Rozga J, Moscioni AD, Ro MS, Hakim R, Arnaout WS and Demetriou AA. Use of a novel bioartiflcial liver in a patient with acute liver insufficiency. Surgery 1993; 113: 340–343.

    PubMed  CAS  Google Scholar 

  28. Rozga J, Podesta L, Lepage E, Morsiani E, Moscioni AD, Hoffman A, Sher L, Villamil F, Woolf G and McGrath M. A bioartificial liver to treat severe acute liver failure. Ann Surg 1994; 219: 538–544.

    Article  PubMed  CAS  Google Scholar 

  29. Stevens C and Demetriou AA. An interim analysis of a phase II/III prospective randomized, multicenter, controlled trial of the HepatAssist bioartificial liver support system for the treatment of fulminant hepatic failure. Hepatology 2001; 34, 299a. (abstract)

    Article  Google Scholar 

  30. Xue YL, Zhao SF, Luo Y, Li XJ, Duan ZP, Chen XP, Li WG, Huang XQ, Li YL, Cui X, Zhong DG, Zhang ZY and Huang ZQ. TECA hybrid artificial liver support system in treatment of acute liver failure. World J Gastroenterol 2001; 7: 826–829.

    PubMed  CAS  Google Scholar 

  31. Chen XP, Xue YL, Li XJ, Zhang ZY, Li YL and Huang ZQ. Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure. World J Gastroenterol 2001; 7: 706–709.

    PubMed  CAS  Google Scholar 

  32. Patzer JF, Mazariegos GV, Lopez R, Molmenti E, Gerber D, Riddervold F, Khanna A, Yin WY, Chen Y, Scott VL, Aggarwal S, Kramer DJ, Wagner RA, Zhu Y, Fulmer ML, Block GD and Amiot BP. Novel bioartificial liver support system: preclinical evaluation. Ann N Y Acad Sci 1999; 875: 340–352.

    Article  PubMed  Google Scholar 

  33. Mazariegos GV, Kramer DJ, Lopez RC, Shakil AO, Rosenbloom AJ, DeVera M, Giraldo M, Grogan TA, Zhu Y, Fulmer ML, Amiot BP and Patzer JF. Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial liver Support System after the first four patients. ASAIO J 2001; 47: 471–475.

    Article  PubMed  CAS  Google Scholar 

  34. Morsiani E, Brogli M, Galavotti D, Bellini T, Ricci D, Pazzi P and Puviani AC. Long-term expression of highly differentiated functions by isolated porcine hepatocytes perfused in a radial-flow bioreactor. Artif Organs 2001; 25: 740–748.

    Article  PubMed  CAS  Google Scholar 

  35. Morsiani E, Pazzi P, Puviani AC, Brogli M, Varied L, Gorini P, Scoletta P, Marangoni E, Ragazzi R, Azzena G, Frazzoli E, Di Luca D, Cassai E, Lombardi G, Cavallari A, Faenza S, Pasetto A, Girardis M, Jovine E and Pinna AD. Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients. Int J Artif Organs 2002; 25: 192–202.

    PubMed  CAS  Google Scholar 

  36. Gerlach JC. Development of a hybrid liver support system: a review. Int J Artif Organs 1996; 19: 645–654.

    PubMed  CAS  Google Scholar 

  37. Sauer M, Obermeyer N, Kardassis D, Theruvath T and Gerlach JC. Development of a hybrid liver support system. Ann N Y Acad Sci 2001; 944: 308–319.

    Article  PubMed  CAS  Google Scholar 

  38. Mundt A, Puhl G, Muller A, Sauer I, Muller C, Richard R, Fotopoulou C, Doll R, Gabelein G, Hohn W, Hofbauer R, Neuhaus P and Gerlach J. A method to assess biochemical activity of liver cells during clinical application of extracorporeal hybrid liver support. Int J Artif Organs 2002; 25: 542–548.

    PubMed  CAS  Google Scholar 

  39. Flendrig LM, te Velde AA and Chamuleau RA. Semipermeable hollow fiber membranes in hepatocyte bioreactors: a prerequisite for a successful bioartificial liver?. Artif Organs 1997; 21: 1177–1181.

    Article  PubMed  CAS  Google Scholar 

  40. Flendrig LM, la SJ, Jorning GG, Steenbeek A, Karlsen OT, Bovee, WM, Ladiges NC, te Velde AA and Chamuleau RA. In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates. J Hepatol 1997; 26: 1379–1392.

    Article  PubMed  CAS  Google Scholar 

  41. Flendrig LM, Sommeijer D, Ladiges NC, te Velde AA, Maas MA, Jorning, GG, Daalhuisen J and Chamuleau RA. Commercially available media for flushing extracorporeal bioartificial liver systems prior to connection to the patient’s circulation: an in vitro comparative study in two and three dimensional porcine hepatocyte cultures. Int J Artif Organs 1998; 21: 467–472.

    PubMed  CAS  Google Scholar 

  42. Flendrig LM, Maas MA, Daalhuisen J, Ladiges NC, la Sou J, Te Velde AA and Chamuleau RA. Does the extent of the culture time of primary hepatocytes in a bioreactor affect the treatment efficacy of a bioartificial liver? Int J Artif Organs 1998; 21: 542–547.

    PubMed  CAS  Google Scholar 

  43. Flendrig LM, Chamuleau RA, Maas MA, Daalhuisen J, Hasset B, Kilty CG, Doyle S, Ladiges NC, Jorning GG, la SJ, Sommeijer D and te Velde AA. Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability. J Hepatol 1999; 30: 311–320.

    Article  PubMed  CAS  Google Scholar 

  44. Flendrig LM, Calise F, Di Florio E, Mancini A, Ceriello A, Santaniello W, Mezza E, Sicolo F, Belleza G, Bracco A, Cozzolino S, Scala D, Mazzone M, Fattore M, Gonzales E and Chamuleau RAFM. Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver. Internat J Artif Org 1999; 22: 701–708.

    CAS  Google Scholar 

  45. Sosef MN, van de Kerkhove MP, Abrahamse LS, Levi M, Chamuleau RA and van Gulik TM. Blood coagulation in anhepatic pigs: Effects of treatment with the AMC bioartificial liver. Thromb & Hemost 2002; in press.

    Google Scholar 

  46. van de Kerkhove MP, Di Florio E, Scuderi V, Mancini A, Belli A, Bracco A, Dauri M, Tisone G, Di Nicuolo G, Amoroso P, Spadari A, Lombardi G, Hoekstra R, Calise F and Chamuleau RA. Phase I clinical trial with the AMC-Bioartificial liver. Intern J Artif Organs 2002; 25: 950–959.

    Google Scholar 

  47. Sosef MN, Abrahamse LS, van de Kerkhove MP, Hartman R, Chamuleau RA and van Gulik TM. Assessment of the AMC-bioartificial liver in the anhepatic pig. Transplantation 2002; 73: 204–209.

    Article  PubMed  CAS  Google Scholar 

  48. Abrahamse LS, van de Kerkhove MP, Sosef MN, Hartman R, Chamuleau RA and van Gulik TM. Treatment of acute liver failure in pigs reduces hepatocyte function in a bioartificial liver support system. Intern J Artif Organs 2002; 25: 966–974.

    CAS  Google Scholar 

  49. Donini A, Baccarani U, Risaliti A, Degrassi A and Bresadola F. Temporary neurological improvement in a patient with acute or chronic liver failure treated with a bioartificial liver device. Am J Gastroenterol 2000; 95:1102–1104.

    Article  PubMed  CAS  Google Scholar 

  50. Crepaldi G, Demetriou AA and Muraca M. Experience in design of controlled clinical trials in acute liver failure. In Riordan SM and Williams R (Eds). Bioartificial Liver Support Systems. Rome: CIC Edizioni Internazionali; 1997: 104–115.

    Google Scholar 

  51. O’Grady JG, Alexander GJ, Hayllar KM and Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439–445.

    PubMed  Google Scholar 

  52. Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, Degott C, Bezeaud A, Rueff B and Benhamou JP. Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology 1986; 6:648–651.

    Article  PubMed  CAS  Google Scholar 

  53. Khalili TM, Navarro A, Ting P, Kamohara Y, Arkadopoulos N, Solomon BA, Demetriou AA and Rozga J. Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure. Artif Organs 2001; 25: 566–570.

    Article  PubMed  CAS  Google Scholar 

  54. Suh KS, Lilja H, Kamohara Y, Eguchi S, Arkadopoulos N, Neuman T, Demetriou AA and Rozga J. Bioartificial liver treatment in rats with fulminant hepatic failure: effect on DNA-binding activity of liver-enriched and growth-associated transcription factors. J Surg Res 1999; 85: 243–250.

    Article  PubMed  CAS  Google Scholar 

  55. Gerlach JC, Lemmens P, Schon M, Janke J, Rossaint R, Busse B, Puhl G and Neuhaus P. Experimental evaluation of a hybrid liver support system. Transplant Proc 1997; 29: 852.

    Article  PubMed  CAS  Google Scholar 

  56. Hughes RD and Williams R. Evaluation of extracorporeal bioartificial liver devices. Liver Transpl Surg 1995; 1:200–206.

    Article  PubMed  CAS  Google Scholar 

  57. Stoves J, Goode NP, Visvanathan R, Jones CH, Shires M, Will EJ and Davison AM. The bradykinin response and early hypotension at the introduction of continuous renal replacement therapy in the intensive care unit. Artif Organs 2001; 25: 1009–1013.

    Article  PubMed  CAS  Google Scholar 

  58. Pitkin Z and Mullon C. Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system. Artif Organs 1999; 23: 829–833.

    Article  PubMed  CAS  Google Scholar 

  59. Pitkin Z, Switzer W, Stevens AC, Solomon B, Shanmugam V, Bhullar V, Hussain A, Matthews A, Sandstrom P and Heneine W. An interim analysis of PERV infectivity in 74 patients treated with a bioartificial liver in a prospective, randomized, multicenter controlled trial. Hepatology 2002; 34: 249a.

    Google Scholar 

  60. Hoekstra R and Chamuleau RA. Recent developments on human cell lines for the bioartificial liver. Int J Artif Organs 2002; 25: 182–191.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Surgical Laboratory, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands

    M-P van de Kerkhove & T. M. van Gulik

  2. Department of Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    R. A. F. M. Chamuleau

Authors
  1. M-P van de Kerkhove
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. A. F. M. Chamuleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. M. van Gulik
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

    E. Anthony Jones  & Robert A. F. M. Chamuleau  & 

  2. Department of Biochemistry, Academic Medical Center, Amsterdam, Netherlands

    Alfred J. Meijer

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

van de Kerkhove, MP., Chamuleau, R.A.F.M., van Gulik, T.M. (2003). Clinical application of bioartificial liver support systems. In: Jones, E.A., Meijer, A.J., Chamuleau, R.A.F.M. (eds) Encephalopathy and Nitrogen Metabolism in Liver Failure. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0159-5_38

Download citation

  • DOI: https://doi.org/10.1007/978-94-010-0159-5_38

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-3967-3

  • Online ISBN: 978-94-010-0159-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation