New Liver Support Devices in Acute Liver Failure: A Critical Evaluation

Sambit Sen; Roger Williams

doi:10.1055/s-2003-42646

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2003; 23(3): 283-294
DOI: 10.1055/s-2003-42646

New Liver Support Devices in Acute Liver Failure: A Critical Evaluation

Sambit Sen² , Roger Williams^1,2

¹Professor of Hepatology Director,Institute of Hepatology University College London University College London Hospitals London, United Kingdom
²Institute of Hepatology, University College London and University College London Hospitals, London, United Kingdom

Abstract

ABSTRACT

Acute liver failure remains a condition with substantial mortality in spite of the best available medical care. Liver transplantation is often not possible or delayed, and liver support systems can be used to maintain the patient during the crisis by bridging to transplantation or allowing recovery of the native liver. Bioartificial devices, using porcine or human hepatocytes, have yielded encouraging results on consciousness levels in a number of studies and have generally been found to be safe, although in one large controlled trial reported to date, benefit was restricted to certain subgroups. Artificial devices, like those based on albumin dialysis, are undoubtedly effective in removing protein-bound toxins, and uncontrolled evidence shows some survival benefit. The large multicenter controlled trials necessary for proving the value of these systems are difficult to design. They have to take into account the influence of transplantation, etiology, and other factors on outcome. Achieving a standard medical regime for these critically ill patients between different centers is also difficult.

KEYWORDS

Extracorporeal - bioartificial - hepatocytes - albumin dialysis

Full Text

References

REFERENCES

1 Stockmann H B, IJzermans J N. Prospects for the temporary treatment of acute liver failure. Eur J Gastroenterol Hepatol . 2002; 14 195-203
2 Miwa S, Hashikura Y, Mita A. et al . Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure. Hepatology . 1999; 30 1521-1526
3 Baker A, Dhawan A, Devlin J. et al . Assessment of potential donors for living related liver transplantation. Br J Surg . 1999; 86 200-205
4 Abouna G M. Cross-circulation between man and baboon in hepatic coma. Lancet . 1968; 2 729-730
5 Motin J, Bouletreau P, Petit P, Latarjet J. Hepatic assistance by means of inter-human cross circulation. Apropos of 6 cases. Minerva Chir . 1974; 29 989-993
6 Abouna G M, Garry R, Hull C. et al . Pig-liver perfusion in hepatic coma. Lancet . 1968; 2 509-510
7 Ranek L, Hansen R I, Hilden M. et al . Pig liver perfusion in the treatment of acute hepatic failure. Scand J Gastroenterol Suppl . 1971; 9 161-169
8 Graw Jr G R, Buckner C D, Eisel R. Plasma exchange transfusion for hepatic coma. New technic. Transfusion . 1970; 10 26-32
9 Larsen F S, Hansen B A, Jorgensen L G. et al . High-volume plasmapheresis and acute liver transplantation in fulminant hepatic failure. Transplant Proc . 1994; 26 1788
10 Clemmesen J O, Kondrup J, Nielsen L B. et al . Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure. Am J Gastroenterol . 2001; 96 1217-1223
11 Clemmesen J O, Larsen F S, Ejlersen E. et al . Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure. Eur J Gastroenterol Hepatol . 1997; 9 55-60
12 Larsen F S, Hansen B A, 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; 8 261-265
13 O'Grady J G, Gimson A E, O'Brien C J. et al . Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology . 1988; 94 1186-1192
14 McGuire B M, Sielaff T D, Nyberg S L. et al . Review of support systems used in the management of fulminant hepatic failure. Dig Dis . 1995; 13 379-388
15 Allen J W, Hassanein T, Bhatia S N. Advances in bioartificial liver devices. Hepatology . 2001; 34 447-455
16 Jauregui H O, Mullon C J, Trenkler D. et al . In vivo evaluation of a hollow fiber liver assist device. Hepatology . 1995; 21 460-469
17 Nyberg S L, Peshwa M V, Payne W D. et al . Evolution of the bioartificial liver: the need for randomized clinical trials. Am J Surg . 1993; 166 512-521
18 Sussman N L, Chong M G, Koussayer T. et al . Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology . 1992; 16 60-65
19 Rozga J, Williams F, Ro M S. et al . Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells. Hepatology . 1993; 17 258-265
20 Flendrig L M, Calise F, Di Florio E. et al . Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver. Int J Artif Organs . 1999; 22 701-709
21 Sosef M N, Abrahamse L S, van de Kerkhove P M. et al . Assessment of the AMC-bioartificial liver in the anhepatic pig. Transplantation . 2002; 73 204-209
22 Arai K, Lee K, Berthiaume F. et al . Intrahepatic amino acid and glucose metabolism in a D-galactosamine-induced rat liver failure model. Hepatology . 2001; 34 360-371
23 Sen S, Williams R, Jalan R. The pathophysiological basis of acute-on-chronic liver failure. Liver . 2002; 22(Suppl 2) 5-13
24 Hughes R D, Cochrane A M, Thomson A D. et al . The cytotoxicity of plasma from patients with acute hepatic failure to isolated rabbit hepatocytes. Br J Exp Pathol . 1976; 57 348-353
25 Suh K S, Lilja H, Kamohara Y. et al . 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
26 Strain A J, Neuberger J M. A bioartificial liver-state of the art. Science . 2002; 295 1005-1009
27 Nagasue N, Yukaya H, Ogawa Y. et al . Human liver regeneration after major hepatic resection. A study of normal liver and livers with chronic hepatitis and cirrhosis. Ann Surg . 1987; 206 30-39
28 Arkadopoulos N, Lilja H, Suh K S. et al . Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats. Hepatology . 1998; 28 1365-1370
29 Wu L, Sun J, Wang L. et al . Cryopreservation of primary porcine hepatocytes for use in bioartificial liver support systems. Transplant Proc . 2000; 32 2271-2272
30 Yagi T, Hardin J A, Valenzuela Y M. et al . Caspase inhibition reduces apoptotic death of cryopreserved porcine hepatocytes. Hepatology . 2001; 33 1432-1440
31 Kono Y, Yang S, Letarte M, Roberts E A. Establishment of a human hepatocyte line derived from primary culture in a collagen gel sandwich culture system. Exp Cell Res . 1995; 221 478-485
32 McCloskey P, Edwards R J, Tootle R. et al . Resistance of three immortalized human hepatocyte cell lines to acetaminophen and N-acetyl-p-benzoquinoneimine toxicity. J Hepatol . 1999; 31 841-81
33 McCloskey P, Tootle R, Selden C. et al . Modulation of hepatocyte function in an immortalized human hepatocyte cell line following exposure to liver-failure plasma. Artif Organs . 2002; 26 340-348
34 Gerlach J C, Schnoy N, Encke J. et al . Improved hepatocyte in vitro maintenance in a culture model with woven multicompartment capillary systems: electron microscopy studies. Hepatology . 1995; 22 546-552
35 Flendrig L M, la Soe W J, Jorning G G. et al . 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
36 Morsiani E, Pazzi P, Puviani A C. et al . Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients. Int J Artif Organs . 2002; 25 192-202
37 Riordan S M, Williams R. Acute liver failure: targeted artificial and hepatocyte-based support of liver regeneration and reversal of multiorgan failure. J Hepatol . 2000; 32(Suppl 1) 63-76
38 Matsumura K N, Guevara G R, Huston H. et al . Hybrid bioartificial liver in hepatic failure: preliminary clinical report. Surgery . 1987; 101 99-103
39 Chen S C, Hewitt W R, Watanabe F D. et al . Clinical experience with a porcine hepatocyte-based liver support system. Int J Artif Organs . 1996; 19 664-669
40 Watanabe F D, Mullon C J, Hewitt W R. et al . Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Ann Surg . 1997; 225 484-491
41 Samuel D, Ichai P, Feray C. et al . Neurological improvement during bioartificial liver sessions in patients with acute liver failure awaiting transplantation. Transplantation . 2002; 73 257-264
42 Stevens A C, Busuttil R, Han S. et al . An interim analysis of a phase II/III prospective randomized, multicenter, controlled trial of the Hepatassist(R) bioartificial liver support system for the treatment of fulminant hepatic failure (Abst). Hepatology . 2001; 34 299A
43 Ellis A J, Hughes R D, Wendon J A. et al . Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology . 1996; 24 1446-1451
44 Millis J M, Kramer D J, O'Grady J. et al . Results of phase I trial of the extracorporeal liver assist device for patients with fulminant hepatic failure. Am J Transplantation . 2001; 1(Suppl 1) 391
45 van de Kerkhove P M, Di Florio E, Scuderi V. et al . Phase I clinical trial with the AMC-bioartificial liver. Academic Medical Center. Int J Artif Organs . 2002; 25 950-959
46 Sauer I M, Zeilinger K, Obermayer N. et al . Primary human liver cells as source for modular extracorporeal liver support-a preliminary report. Int J Artif Organs . 2002; 25 1001-1005
47 Mundt A, Puhl G, Muller A. et al . 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
48 Sauer I M, Kardassis D, Zeillinger K. et al . Clinical extracorporeal hybrid liver support-phase I study with primary porcine liver cells (in press). Xenotransplantation . 2003;
49 Jalan R, Williams R. Bio-artificial liver support for acute liver failure: should we be using it to treat patients?. Transplantation . 2002; 73 165-166
50 Baquerizo A, Mhoyan A, Shirwan H. et al . Xenoantibody response of patients with severe acute liver failure exposed to porcine antigens following treatment with a bioartificial liver. Transplant Proc . 1997; 29 964-965
51 Abouna G M, Boehmig H G, Serrou B. et al . Long-term hepatic support by intermittent multi-species liver perfusions. Lancet . 1970; 2 391-396
52 Nyberg S L, Hibbs J R, Hardin J A. et al . Influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes. Liver Transpl . 2000; 6 76-84
53 Patience C, Takeuchi Y, Weiss R A. Infection of human cells by an endogenous retrovirus of pigs. Nat Med . 1997; 3 282-286
54 Martin U, Kiessig V, Blusch J H. et al . Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet . 1998; 352 692-694
55 Wilson C A, Wong S, Muller J. et al . Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J Virol . 1998; 72 3082-3087
56 Nyberg S L, Hibbs J R, Hardin J A. et al . Transfer of porcine endogenous retrovirus across hollow fiber membranes: significance to a bioartificial liver. Transplantation . 1999; 67 1251-1255
57 Martin U, Winkler M E, Id M. et al . Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV). Xenotransplantation . 2000; 7 138-142
58 Heneine W, Tibell A, Switzer W M. et al . No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet . 1998; 352 695-699
59 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 1236-1241
60 Patience C, Patton G S, Takeuchi Y. et al . No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet . 1998; 352 699-701
61 Mitzner S R, Stange J, Klammt S. et al . Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. J Am Soc Nephrol . 2001; 12(Suppl 17) S75-S82
62 Stange J, Ramlow W, Mitzner S. et al . Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. Artif Organs . 1993; 17 809-813
63 Stange J, Mitzner S. A carrier-mediated transport of toxins in a hybrid membrane. Safety barrier between a patients blood and a bioartificial liver. Int J Artif Organs . 1996; 19 677-691
64 Hughes R, Ton H Y, Langley P. et al . Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part II: in vivo evaluation. Artif Organs . 1979; 3 23-26
65 Stange J, Mitzner S, Ramlow W. et al . A new procedure for the removal of protein bound drugs and toxins. Asaio J . 1993; 39 M621-625
66 Ash S R, Blake D E, Carr D J. et al . Clinical effects of a sorbent suspension dialysis system in treatment of hepatic coma (the BioLogic-DT). Int J Artif Organs . 1992; 15 151-161
67 Ash S R, Blake D E, Carr D J, Harker K D. Push-pull sorbent based pheresis for treatment of acute hepatic failure: the BioLogic-detoxifier/plasma filter System. Asaio J . 1998; 44 129-139
68 Hughes R D, Pucknell A, Routley D. et al . Evaluation of the BioLogic-DT sorbent-suspension dialyser in patients with fulminant hepatic failure. Int J Artif Organs . 1994; 17 657-662
69 Mitzner S R, Klammt S, Peszynski P. et al . Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system. Ther Apher . 2001; 5 417-422
70 Sorkine P, Ben Abraham R, Szold O. et al . Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure. Crit Care Med . 2001; 29 1332-1336
71 Stange J, Mitzner S R, 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; 23 319-330
72 Mitzner S R, Stange J, Klammt S. et al . Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl . 2000; 6 277-286
73 Heemann U, Treichel U, Loock J. et al . Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology . 2002; 36 949-958
74 Novelli G, Rossi M, Pretagostini R. et al . MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure. Liver . 2002; 22(Suppl 2) 43-47
75 Isoniemi H. Current indications for albumin dialysis: acute hepatic failure. In: 4th International Symposium on Albumin Dialysis in Liver Disease Rostock-Warnemunde, Germany: University of Rostock; September 6-8 2002: 21-22
76 Abraham R B, Szold O, Merhav H. et al . Rapid resolution of brain edema and improved cerebral perfusion pressure following the molecular adsorbent recycling system in acute liver failure patients. Transplant Proc . 2001; 33 2897-2899
77 Awad S S, Swaniker F, Magee J. et al . Results of a phase I trial evaluating a liver support device utilizing albumin dialysis. Surgery . 2001; 130 354-362
78 Lamesch P, Jost U, Schreiter D. et al . Molecular adsorbant recirculating system in patients with liver failure. Transplant Proc . 2001; 33 3480-482
79 Manz T, Bisse E, Ochs A. et al . MARS for treatment of fulminant Wilson crisis. Z Gastroenterol . 2001; 39(Suppl) 49
80 Sen S, Felldin M, Steiner C. et al . Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease. Liver Transplantation . 2002; 8 962-967
81 Kreymann B, Seige M, Schweigart U. et al . 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 1080-1085
82 McIntyre C W, Fluck R J, Freeman J G, Lambie S H. Use of albumin dialysis in the treatment of hepatic and renal dysfunction due to paracetamol intoxication. Nephrol Dial Transplant . 2002; 17 316-317
83 Siewert-Delle A, Henriksson B A, Baeckmann L. Albumin dialysis with the MARS for a patient with acute liver failure due to paracetamol intoxication: a case report. Z Gastroenterol . 2001; 39(Suppl) 48
84 Shi Y, He J, Chen S. et al . MARS: optimistic therapy method in fulminant hepatic failure secondary to cytotoxic mushroom poisoning-a case report. Liver . 2002; 22(Suppl 2) 78-80
85 Steiner C, Mitzner S. Experiences with MARS liver support therapy in liver failure: analysis of 176 patients of the International MARS Registry. Liver . 2002; 22(Suppl 2) 20-25
86 Mallet V O, Mitchell C, Mezey E. et al . Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo. Hepatology . 2002; 35 799-804
87 Kobayashi N, Fujiwara T, Westerman K A. et al . Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science . 2000; 287 1258-1262
88 Seternes T, Sorensen K, Smedsrod B. Scavenger endothelial cells of vertebrates: a nonperipheral leukocyte system for high-capacity elimination of waste macromolecules. Proc Natl Acad Sci USA . 2002; 99 7594-7597
89 Auth M K, Joplin R E, Okamoto M. et al . Morphogenesis of primary human biliary epithelial cells: induction in high-density culture or by coculture with autologous human hepatocytes. Hepatology . 2001; 33 519-529
90 Sirica A E, Gainey T W. A new rat bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro. Hepatology . 1997; 26 537-549