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Semin Respir Crit Care Med 2012; 33(01): 70-79
DOI: 10.1055/s-0032-1301736
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Liver Replacement Therapy

Giovanni Tritto
1   Liver Failure Group, Institute of Hepatology, University College London Medical School, Royal Free Hospital, London, United Kingdom.
,
Nathan A. Davies
1   Liver Failure Group, Institute of Hepatology, University College London Medical School, Royal Free Hospital, London, United Kingdom.
,
Rajiv Jalan
1   Liver Failure Group, Institute of Hepatology, University College London Medical School, Royal Free Hospital, London, United Kingdom.
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Publikationsdatum:
23. März 2012 (online)

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Abstract

The realization of a support device able to effectively replace liver function in patients with hepatic failure has thus far been an elusive goal. The complexity of liver metabolic, synthetic, detoxifying, and excretory functions make artificial hepatic support extremely challenging. Currently, no specific treatment is available to reverse acute or acute-on-chronic liver failure, and morbidity and mortality of these syndromes are still high. Present management strategies are supportive, while waiting for spontaneous liver regeneration or liver transplant. Because of the scarcity of donor organs, liver support strategies are needed for patients with inadequate liver function until an appropriate organ becomes available for transplantation or until their liver recovers from injury. Currently available liver support systems comprise nonbiological systems (e.g., hemodiafiltration, albumin dialysis, and plasma exchange) and bioartificial systems utilizing viable liver cells. The role for these novel systems and their impact on survival or other clinically important outcomes are controversial. Development and use of bioartificial systems are limited by the inherent cost.

Keywords

liver failure - extracorporeal liver support - albumin dialysis - bioartificial liver
 

  • References

  • 1 O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993; 342 (8866) 273-275
    CrossrefPubMedSuche in Google Scholar
  • 2 O’Grady JG. Acute liver failure. Postgrad Med J 2005; 81 (953) 148-154
    CrossrefPubMedSuche in Google Scholar
  • 3 Jalan R, Williams R. Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif 2002; 20 (3) 252-261
    CrossrefPubMedSuche in Google Scholar
  • 4 Stockmann HB, IJzermans JN. Prospects for the temporary treatment of acute liver failure. Eur J Gastroenterol Hepatol 2002; 14 (2) 195-203
    CrossrefPubMedSuche in Google Scholar
  • 5 Shakil AO, Kramer D, Mazariegos GV, Fung JJ, Rakela J. Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria. Liver Transpl 2000; 6 (2) 163-169
    PubMedSuche in Google Scholar
  • 6 Jalan R, Sen S. Extracorporeal albumin dialysis for intoxication from protein-bound agents. Crit Care Med 2004; 32 (6) 1436-1437, author reply 1437
    PubMedSuche in Google Scholar
  • 7 McGuire BM, Sielaff TD, Nyberg SL, Hu MY, Cerra FB, Bloomer JR. Review of support systems used in the management of fulminant hepatic failure. Dig Dis 1995; 13 (6) 379-388
    CrossrefPubMedSuche in Google Scholar
  • 8 Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60 (8) 646-649
    CrossrefPubMedSuche in Google Scholar
  • 9 Ginès A, Fernández-Esparrach G, Monescillo A , et al. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology 1996; 111 (4) 1002-1010
    CrossrefPubMedSuche in Google Scholar
  • 10 Sort P, Navasa M, Arroyo V , et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341 (6) 403-409
    CrossrefPubMedSuche in Google Scholar
  • 11 Ortega R, Ginès P, Uriz J , et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology 2002; 36 (4 Pt 1) 941-948
    CrossrefPubMedSuche in Google Scholar
  • 12 Jalan R, Schnurr K, Mookerjee RP , et al. Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. Hepatology 2009; 50 (2) 555-564
    PubMedSuche in Google Scholar
  • 13 Stange J, Mitzner SR, Risler T , et al. Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support. Artif Organs 1999; 23 (4) 319-330
    CrossrefPubMedSuche in Google Scholar
  • 14 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 (9) 809-813
    CrossrefPubMedSuche in Google Scholar
  • 15 Mitzner S, Loock J, Peszynski P , et al. Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS—a review of clinical, biochemical, and electrophysiological data. Metab Brain Dis 2002; 17 (4) 463-475
    CrossrefPubMedSuche in Google Scholar
  • 16 Sen S, Ytrebø LM, Rose C , et al. Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs. Intensive Care Med 2004; 30 (3) 496-501
    CrossrefPubMedSuche in Google Scholar
  • 17 Stange J, Mitzner S, Ramlow W, Gliesche T, Hickstein H, Schmidt R. A new procedure for the removal of protein bound drugs and toxins. ASAIO J 1993; 39 (3) M621-M625
    PubMedSuche in Google Scholar
  • 18 Sen S, Davies NA, Mookerjee RP , et al. Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl 2004; 10 (9) 1109-1119
    CrossrefPubMedSuche in Google Scholar
  • 19 Sen S, Ratnaraj N, Davies NA , et al. Treatment of phenytoin toxicity by the Molecular Adsorbents Recirculating System (MARS). Epilepsia 2003; 44 (2) 265-267
    CrossrefPubMedSuche in Google Scholar
  • 20 Stadlbauer V, Krisper P, Aigner R , et al. Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure. Crit Care 2006; 10 (6) R169
    CrossrefPubMedSuche in Google Scholar
  • 21 Saliba F, Camus C, Durand F , et al. Predictive factors of transplant free survival in patients with fulminant and subfulminant liver failure: results from a randomized controlled multicenter trial [abstract]. J Hepatol 2009; 50 (S1) S89
    PubMedSuche in Google Scholar
  • 22 Khuroo MS, Khuroo MS, Farahat KL. Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis. Liver Transpl 2004; 10 (9) 1099-1106
    CrossrefPubMedSuche in Google Scholar
  • 23 Banares R, Nevens F, Larsen FS , et al. Extracorporeal liver support with the molecular adsorbent recirculating system (MARS) in patients with acute-on-chronic liver failure (AOLF). The RELIEF trial [abstract]. J Hepatol 2010; 52: A1184
    PubMedSuche in Google Scholar
  • 24 Rifai K, Ernst T, Kretschmer U , et al. Prometheus—a new extracorporeal system for the treatment of liver failure. J Hepatol 2003; 39 (6) 984-990
    CrossrefPubMedSuche in Google Scholar
  • 25 McKenzie TJ, Lillegard JB, Nyberg SL. Artificial and bioartificial liver support. Semin Liver Dis 2008; 28 (2) 210-217
    Thieme ConnectPubMedSuche in Google Scholar
  • 26 Evenepoel P, Laleman W, Wilmer A , et al. Prometheus versus molecular adsorbents recirculating system: comparison of efficiency in two different liver detoxification devices. Artif Organs 2006; 30 (4) 276-284
    CrossrefPubMedSuche in Google Scholar
  • 27 Laleman W, Wilmer A, Evenepoel P , 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
    CrossrefPubMedSuche in Google Scholar
  • 28 Rifai K, Kribben A, Gerken G , et al. Extracorporeal liver support by fractioned plasma separation and adsorption (Prometheus) in patients with acute-on-chronic liver failure (HELIOS study): a prospective randomized controlled multicenter study [abstract]. J Hepatol 2010; 52: S3
    PubMedSuche in Google Scholar
  • 29 Peszynski P, Klammt S, Peters E, Mitzner S, Stange J, Schmidt R. Albumin dialysis: single pass vs. recirculation (MARS). Liver 2002; 22 (Suppl) (2) 40-42
    PubMedSuche in Google Scholar
  • 30 Sauer IM, Goetz M, Steffen I , et al. In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD). Hepatology 2004; 39 (5) 1408-1414
    CrossrefPubMedSuche in Google Scholar
  • 31 Karvellas CJ, Bagshaw SM, McDermid RC, Stollery DE, Bain VG, Gibney RT. A case-control study of single-pass albumin dialysis for acetaminophen-induced acute liver failure. Blood Purif 2009; 28 (3) 151-158
    CrossrefPubMedSuche in Google Scholar
  • 32 Rozga J, Umehara Y, Trofimenko A, Sadahiro T, Demetriou AA. A novel plasma filtration therapy for hepatic failure: preclinical studies. Ther Apher Dial 2006; 10 (2) 138-144
    CrossrefPubMedSuche in Google Scholar
  • 33 Clemmesen JO, Gerbes AL, Gülberg V , et al. Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis. Hepatology 1999; 29 (2) 347-355
    CrossrefPubMedSuche in Google Scholar
  • 34 Larsen FS, Hansen BA, Ejlersen E , et al. Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant hepatic failure. Eur J Gastroenterol Hepatol 1996; 8 (3) 261-265
    CrossrefPubMedSuche in Google Scholar
  • 35 Larsen FS, Schmidt LE, Wendon J , et al. Liver assisting with high-volume plasma exchange in patients with acute liver failure [abstract]. Hepatology 2010; 52: 376A
    PubMedSuche in Google Scholar
  • 36 Mookerjee RP, Stadlbauer V, Lidder S , et al. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. Hepatology 2007; 46 (3) 831-840
    CrossrefPubMedSuche in Google Scholar
  • 37 Stadlbauer V, Mookerjee RP, Hodges S, Wright GA, Davies NA, Jalan R. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J Hepatol 2008; 48 (6) 945-951
    CrossrefPubMedSuche in Google Scholar
  • 38 Chamuleau RA, Deurholt T, Hoekstra R. Which are the right cells to be used in a bioartificial liver?. Metab Brain Dis 2005; 20 (4) 327-335
    CrossrefPubMedSuche in Google Scholar
  • 39 Strain AJ, Neuberger JM. A bioartificial liver—state of the art. Science 2002; 295 (5557) 1005-1009
    CrossrefPubMedSuche in Google Scholar
  • 40 Allen JW, Hassanein T, Bhatia SN. Advances in bioartificial liver devices. Hepatology 2001; 34 (3) 447-455
    CrossrefPubMedSuche in Google Scholar
  • 41 Kobayashi N, Fujiwara T, Westerman KA , et al. Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science 2000; 287 (5456) 1258-1262
    CrossrefPubMedSuche in Google Scholar
  • 42 Totsugawa T, Yong C, Rivas-Carrillo JD , et al. Survival of liver failure pigs by transplantation of reversibly immortalized human hepatocytes with Tamoxifen-mediated self-recombination. J Hepatol 2007; 47 (1) 74-82
    CrossrefPubMedSuche in Google Scholar
  • 43 Chen Y, Soto-Gutierrez A, Navarro-Alvarez N, Basma H, Fox IJ. Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF. Cell Transplant 2007; 16 (1) 97
    PubMedSuche in Google Scholar
  • 44 Soto-Gutierrez A, Navarro-Alvarez N, Rivas-Carrillo JD , et al. Differentiation of human embryonic stem cells to hepatocytes using deleted variant of HGF and poly-amino-urethane-coated nonwoven polytetrafluoroethylene fabric. Cell Transplant 2006; 15 (4) 335-341
    CrossrefPubMedSuche in Google Scholar
  • 45 Watanabe FD, Mullon CJ, Hewitt WR , et al. Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Ann Surg 1997; 225 (5) 484-491 , discussion 491–494
    CrossrefPubMedSuche in Google Scholar
  • 46 Demetriou AA, Brown Jr RS, Busuttil RW , et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg 2004; 239 (5) 660-667 , discussion 667–670
    CrossrefPubMedSuche in Google Scholar
  • 47 van de Kerkhove MP, Di Florio E, Scuderi V , et al. Phase I clinical trial with the AMC-bioartificial liver. Int J Artif Organs 2002; 25 (10) 950-959
    PubMedSuche in Google Scholar
  • 48 Sauer IM, Kardassis D, Zeillinger K , et al. Clinical extracorporeal hybrid liver support—phase I study with primary porcine liver cells. Xenotransplantation 2003; 10 (5) 460-469
    CrossrefPubMedSuche in Google Scholar
  • 49 Mazariegos GV, Patzer II JF, Lopez RC , et al. First clinical use of a novel bioartificial liver support system (BLSS). Am J Transplant 2002; 2 (3) 260-266
    CrossrefPubMedSuche in Google Scholar
  • 50 Di Nicuolo G, van de Kerkhove MP, Hoekstra R , et al. No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC-bioartificial liver. Xenotransplantation 2005; 12 (4) 286-292
    CrossrefPubMedSuche in Google Scholar
  • 51 Paradis K, Langford G, Long Z , et al. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science 1999; 285 (5431) 1236-1241
    CrossrefPubMedSuche in Google Scholar
  • 52 Pitkin Z, Mullon C. Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system. Artif Organs 1999; 23 (9) 829-833
    CrossrefPubMedSuche in Google Scholar
  • 53 Millis JM, Cronin DC, Johnson R , et al. Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure: system modifications and clinical impact. Transplantation 2002; 74 (12) 1735-1746
    PubMedSuche in Google Scholar
  • 54 Miwa Y, Ellis AJ, Hughes RD, Langley PG, Wendon JA, Williams R. Effect of ELAD liver support on plasma HGF and TGF-beta 1 in acute liver failure. Int J Artif Organs 1996; 19 (4) 240-244
    PubMedSuche in Google Scholar
  • 55 Sussman NL, Chong MG, Koussayer T , et al. Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology 1992; 16 (1) 60-65
    CrossrefPubMedSuche in Google Scholar
  • 56 Ellis AJ, Hughes RD, Wendon JA , et al. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology 1996; 24 (6) 1446-1451
    CrossrefPubMedSuche in Google Scholar
  • 57 Zhong-Ping Duan JZ, Xin X, Chen JM , et al. Interim results of randomized controlled trial of ELAD in acute on chronic liver disease [abstract]. Hepatology 2007; 46: 274A
    PubMedSuche in Google Scholar
  • 58 O’Grady JG, Gimson AE, O’Brien CJ, Pucknell A, Hughes RD, Williams R. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 1988; 94 (5 Pt 1) 1186-1192
    PubMedSuche in Google Scholar