Subscribe to RSS
DOI: 10.1055/s-2001-919020
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York
Methods of Extracorporeal Liver Support For Treatment of Liver Cell Failure
Publication History
Publication Date:
07 October 2005 (online)

Introduction
Acute liver cell failure (ALCF), either fulminant or acute on chronic, is associated to an exceedingly high mortality. Historically, two major types of devices have been conceived based either on mechanical or biological replacement of liver functions. Mechanical models lacked metabolic activity and appeared inefficient for detoxifying the plasma, while Biological models developed for ”global” replacement of liver functions were abandoned because of the development of liver transplantation (LT) that became the treatment of choice. Nowadays, because of organ shortage and because fulminant hepatitis (FH) is potentially reversible, a renewed interest has developed in liver support devices to bridge ALCF patients either to LT or regeneration. These liver support devices were conceived according to two different hypotheses of the cause(s) of liver cell failure: the ”albumin-bound toxin hypothesis” and the ”metabolic support hypothesis”.
In this review, we will present the development and progress in extracorporeal liver support systems in the successive decades.
References
- 1
Kiley J, Welch H, Pender J, Welch C.
Removal of blood ammonia by hemodialysis.
Proc Soc Exp Biol Med.
1956;
91
489-490
MissingFormLabel
- 2
Kiley J E, Pender J C, Welch H F, Welch C S.
Ammonia intoxication treated by hemodialysis.
N Engl J Med.
1958;
259
1156-61
MissingFormLabel
- 3
Knell A, Dukes D.
Dialysis procedures in acute liver coma.
Lancet.
1976;
2
402-403
(7982)
MissingFormLabel
- 4
Opolon P, Rapin J R, Huguet C, Granger A, Delorme M L, Boschat M, Sausse A.
Hepatic failure coma (HFC) treated by acrylonitrite membrane (PAN) hemodialysis (HD).
Trans Am Soc Artif Intern Organs.
1976;
22
701-710
MissingFormLabel
- 5
Denis J, Opolon O, Delorme M, Granger A, Darnis F.
Long term extracorporeal assistance by continuous hæmofiltration during fulminant
hepatic failure.
Gastroenterol Clin Biol.
1979;
3
337-348
MissingFormLabel
- 6
Lee C, Tink A.
Exchange transfusion in hepatic coma: Report of a case.
Med J Aust.
1958;
1
40-42
MissingFormLabel
- 7
Trey C, Burns D, Saunders S.
Treatment of hepatic coma by exchange blood transfusion.
N Engl J Med.
1966;
274
473-481
MissingFormLabel
- 8
McKechnie J, Hersh T.
Exchange transfusion in hepatic coma. A review of 19 cases.
Am J Gastroenterol.
1971;
56
17-43
MissingFormLabel
- 9
Redeker A, Yamahiro H.
Controlled trial of exchange-transfusion therapy in fulminant hepatitis.
Lancet.
1973;
1
3-6
(7793)
MissingFormLabel
- 10
Sabin S, Merritt J A.
Treatment of hepatic coma in cirrhosis by plasmapheresis and plasma infusion (plasma
exchange).
Ann Intern Med.
1968;
68
1-7
MissingFormLabel
- 11
Lepore M, Stutman L, Bonanno C, Conklin E, Robilotti-Jr J, MxKenna P.
Plasmapheresis with plasma exchange in hepatic coma. II. Fulminant viral hepatitis
as a systemic disease.
Arch Intern Med.
1972;
129
900-907
MissingFormLabel
- 12
Haapanen E, Tiula E.
Plasmapheresis with albumin as main sustitute in acute hepatic coma.
Scand J Gastroenterol.
1972;
7
75-83
MissingFormLabel
- 13
Matsubara S, Okabe K, Ouchi K, Miyazaki Y, Yajima Y, Suzuki H, Otsuki M, Matsuno S.
Continuous removal of middle molecules by hemofiltration in patients with acute liver
failure.
Crit Care Med.
1990;
18
1331-1338
MissingFormLabel
- 14
Freeman J G, Matthewson K, Record C O.
Plasmapheresis in acute liver failure.
Int J Artif Organs.
1986;
9
433-438
(6)
MissingFormLabel
- 15
Michalopoulos G, Zarnegar R.
Hepatocyte growth factor.
Hepatology.
1992;
15
149-155
MissingFormLabel
- 16
Clemmesen J O, Larsen F S, Ejlersen E, Schiodt F V, Ott P, Hansen B A.
Haemodynamic changes after high-volume plasmapheresis in patients with chronic and
acute liver failure.
Eur J Gastroenterol Hepatol.
1997;
9
55-60
(1)
MissingFormLabel
- 17
Larsen F S, Ejlersen E, Hansen B A, Mogensen T, Tygstrup N, Secher N H.
Systemic vascular resistance during high-volume plasmapheresis in patients with fulminant
hepatic failure: relationship with oxygen consumption.
Eur J Gastroenterol Hepatol.
1995;
7
887-892
(9)
MissingFormLabel
- 18
Larsen F S, Hansen B A, Jorgensen L G, Secher N H, Bondesen S, Linkis P, Hjortrup A, Kirkegaard P, Agerlin N, Kondrup J. et al .
Cerebral blood flow velocity during high volume plasmapheresis in fulminant hepatic
failure.
Int J Artif Organs.
1994;
17
353-361
(6)
MissingFormLabel
- 19
Schechter D, Nealon-Jr T, Gibon-Jr J.
Simple extracorporeal device for lowering elevated blood ammonia levels.
Surgery.
1958;
44
892-897
MissingFormLabel
- 20
Ching N, Nealon-Jr T, Gibbon-Jr J.
An extracorporeal device for hepatic coma.
JAMA.
1963;
183
350-354
MissingFormLabel
- 21
Juggi J.
Extracorporeal cation-exchange circuits in the treatment of hyperammonæmia of hepatic
failure.
Med J Aust.
1973;
60
926-930
MissingFormLabel
- 22
Kawanishi H, Tsuchiya T, Hirabayashi A, Shinhara R, Yamanoue M.
Liver support system used sorbent urethane sheet embeded with powdered charcoal.
Biomater Artif Cells Artif Organs.
1990;
18
535-539
MissingFormLabel
- 23
Visco G, Giannuzzi R, Paglia M, Visco-Comandini U.
Hemoperfusion and liver disease.
Biomater Artif Cells Immobilization Biotechnol.
1993;
21
265-281
MissingFormLabel
- 24
Gimson A, Ede R, Braude S, Hughes R, Langley P, Williams R.
Fulminant hepatic failure and artificial liver support.
Gastroenterol Jpn.
1982;
17
144-162
MissingFormLabel
- 25
Agishi T, Teroaka S, Fuchinoue S, Honda H, Ota K.
An adsorption and filtration technique for temporary hepatic assistance.
ASAIO Trans.
1988;
34
969-971
MissingFormLabel
- 26
Hughes R, Williams R.
Clinical experience with charcoal and resin hemoperfusion.
Semin Liver Dis.
1986;
6
164-173
MissingFormLabel
- 27
O’Grady J, Gimson A, O’Brien C, Pucknell A, Hughes R, Williams R.
Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic
failure.
Gastroenterology.
1988;
94
1186-1192
MissingFormLabel
- 28
Berk P D, Goldberg J D.
Charcoal hemoperfusion. Plus ca change, plus c’est la meme chose.
Gastroenterology.
1988;
94
1228-1230
(5 Pt 1)
MissingFormLabel
- 29
Gimson A E, Langley P G, Hughes R D, Canalese J, Mellon P J, Williams R, Woods H F, Weston M J.
Prostacyclin to prevent platelet activation during charcoal hemoperfusion in fulminant
hepatic failure.
Lancet.
1980;
1
173-175
MissingFormLabel
- 30
Chang T MS.
Hæmoperfusion over a microencapsulated adsorbent in a patient with hepatic coma.
Lancet.
1972;
2
1371-1372
MissingFormLabel
- 31
Gelfand M, Knepshield J, Cohan S, Ramirez B, Schreiner G.
Treatment of hepatic coma with hemoperfusion through polyacrylamide hydrogel coated
charcoal.
Kidney Int.
1976;
10
239-243
MissingFormLabel
- 32
Inoue N.
Approach to hepatic assist utilized in Japan.
Artif Organs.
1988;
12
296-299
MissingFormLabel
- 33
Tabei K, Akai Y, Takeda S, Homma S, Kusano E, Asano Y.
Application of plasma perfusion in hepatic failure.
Biomater Artif Cells Immobilization Biotechnol.
1991;
19
193-201
MissingFormLabel
- 34
Ramos C, Almario J.
Hemodialysis-hemoperfusion in fulminant viral hepatitis.
Biomater Artif Cells Artif Organs.
1990;
18
689-692
MissingFormLabel
- 35
Matsubara S.
Combination of plasma exchange and continuous hemofiltration as temporary metabolic
support for patients with acute liver failure.
Artif Organs.
1994;
18
363-366
(5)
MissingFormLabel
- 36
Ash S.
Hemodiabsorption in treatment of acute hepatic failure and chronic cirrhosis with
ascitis.
Artif Organs.
1994;
18
355-362
(5)
MissingFormLabel
- 37
Kimoto S.
The artificial liver experiments and clinical application.
ASAIO Trans.
1959;
5
102-110
MissingFormLabel
- 38
Burnell J M, Dawborn J K, Epstein R B, Gutman R A, Leinbach G E, Thomas E D, Volwiler W.
Acute hepatic coma treated by cross-circulation or exchange transfusion.
N Engl J Med.
1967;
276
935-943
(17)
MissingFormLabel
- 39
Hollander D, Klebanoff G, Osteen R T.
Human-baboon cross-circulation for treatment of hepatic coma.
JAMA.
1971;
218
67-71
(1)
MissingFormLabel
- 40
Bosman S C, Terblanche J, Saunders S J, Harrison G G, Barnard C N.
Cross-circulation between man and baboon.
Lancet.
1968;
2
583-585
(7568)
MissingFormLabel
- 41
MacDonell Jr R C, Patterson J H, Zwiren G T, Seigler H F, Metzgar R S, Caplan D B, Corrigan Jr J J, Bland Jr J W, Ahmann P A, Behrens B L.
Cross circulation between children in hepatic coma and chimpanzees. Clinical, biochemical,
and coagulation observations.
J Pediatr.
1973;
82
591-597
MissingFormLabel
- 42
Eisman B, Liem D, Raffucci F.
Heterologous liver perfusion in treatment of hepatic failure.
Ann Surg.
1965;
162
329-345
MissingFormLabel
- 43
Abouna G, Fisher L, Porter K, Anders G.
Experience in the treatment of hepatic failure by intermittent liver hemoperfusions.
Surg Gynecol Obstet.
1973;
137
741-752
MissingFormLabel
- 44
Munoz S J, Ballas S K, Moritz M J, Martinez J, Friedman L S, Jarrell B E, Maddrey W C.
Perioperative management of fulminant and subfulminant hepatic failure with therapeutic
plasmapheresis.
Transplant Proc.
1989;
21
3535-3536
(3)
MissingFormLabel
- 45
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
809-813
(9)
MissingFormLabel
- 46
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
(11)
MissingFormLabel
- 47
Stange J, Mitzner S R, Klammt S, Freytag J, Peszynski P, Loock J, Hickstein H, Korten G, Schmidt R, Hentschel J, Schulz M, Lohr M, Liebe S, Schareck W, Hopt U T.
Liver Support by Extracorporeal Blood Purification: A Clinical Observation.
Liver Transpl.
2000;
6
603-613
(5)
MissingFormLabel
- 48
Mitzner S R, Stange J, Klammt S, Risler T, Erley C M, Bader B D, Berger E D, Lauchart W, Peszynski P, Freytag J, Hickstein H, Loock J, Lohr J M, Liebe S, Emmrich J, Korten G, Schmidt R.
Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results
of a prospective, randomized, controlled clinical trial.
Liver Transpl.
2000;
6
277-286
(3)
MissingFormLabel
- 49
Adham M, Peyrol S, Chevallier M, Ducerf C, Vernet M, Barakat C, De La Roche E, Taibi A, Bizollon T, Rigal D, Pouyet M, Baulieux J.
The isolated perfused porcine liver: assessment of viability during and after six
hour perfusion.
Transpl Int.
1997;
10
299-311
MissingFormLabel
- 50
Adham M, Bizollon T, Rigal D, Chevallier M, Peyrol S, Ducerf C, Vernet M, Trepo C, Baulieux J.
Functional and histological assessment of isolated pig liver xenoperfusion with human
blood.
Int J Surg Invest (in Press).
MissingFormLabel
- 51
Fox I J, Langnas A N, Fristoe L W, Shaefer M S, Vogel J E, Antonson D L, Donovan J P, Heffron T G, Markin R S, Sorrell M F. et al .
Successful application of extracorporeal liver perfusion: A technology whose time
has come.
Am J Gastroenterol.
1993;
88
1876-1881
MissingFormLabel
- 52
Chari R S, Collins B H, Magee J C, DiMaio J M, Kirk A D, Harland R C, McCann R L, Platt J L, Meyers W C.
Brief report: Treatment of hepatic failure with exvivo pig-liver perfusion followed
by liver transplantation.
N Engl J Med.
1994;
331
234-237
MissingFormLabel
- 53 ector A, Elias N, Ahmed S. et al. . Ex-vivo pig liver perfusion as a bridge to liver transplantation. (Abstract), ed. Third International Congress for Xenotransplantation. Boston, Massachusetts; USA; 27.September.1995 1.October.1995
MissingFormLabel
- 54
Levy M F, Crippin J, Sutton S, Netto G, McCormack J, Curiel T, Goldstein R M, Newman J T, Gonwa T A, Banchereau J, Diamond L E, Byrne G, Logan J, Klintmalm G B.
Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59)
porcine livers: clinical results and lack of pig-to-human transmission of the porcine
endogenous retrovirus.
Transplantation.
2000;
69
272-280
(2)
MissingFormLabel
- 55
Tector A J, Elias N, Rosenberg L, Soderland C, Naimi J, Duguid W P, Tchervenkov J I.
Mechanism of resistance to injury in pig livers perfused with blood from patients
in liver failure.
Transplant Proc.
1997;
29
966-969
MissingFormLabel
- 56
Adham M, Sab J M, Ducerf C, Tassaux D, Vianey-Saban C, Chevallier M, De La Roche E, v Lê Q, Bizollon T, Barakat C, Debize G, Vernet M, Pouyet M, Baulieux J.
Correction of acute liver cell failure disorders through liver xenoperfusion: experimental
study.
Transplant Proc.
1997;
29
3013-3014
MissingFormLabel
- 57
Sussman N L, Chong M G, Koussayer T, He D E, Shang T A, Whisennand H H, Kelly J H.
Reversal of fulminant hepatic failure using an extracorporeal liver assist device.
Hepatology.
1992;
6
60-65
MissingFormLabel
- 58
Kelly J H, Sussman N L.
The hepatix extracorporeal liver assist device in the treatment of fulminant hepatic
failure.
ASAIO J.
1994;
40
83-85
(1)
MissingFormLabel
- 59
Ellis A J, Hughes R D, Wendon J A, Dunne J, Langley P G, Kelly J H, Gislason G T, Sussman N L, Williams R.
Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.
Hepatology.
1996;
24
1446-1451
(6)
MissingFormLabel
- 60
Neuzil D F, Rozga J, Moscioni A D, Ro M S, Hakim R, Arnaout W S, Demetriou A A.
Use of a novel bioartificial liver in a patient with acute liver insufficiency.
Surgery.
1993;
113
340-343
(3)
MissingFormLabel
- 61
Rozga J, Podesta L, LePage E, Morsiani E, Moscioni A D, Hoffman A, Sher L, Villamil F, Woolf G, McGrath M. et al .
A bioartificial liver to treat severe acute liver failure.
Ann Surg.
1994;
219
538-546
MissingFormLabel
- 62
Watanabe F D, Mullon C J, Hewitt W R, Arkadopoulos N, Kahaku E, Eguchi S, Khalili T, Arnaout W, Shackleton C R, Rozga J, Solomon B, Demetriou A A.
Clinical experience with a bioartificial liver in the treatment of severe liver failure.
A phase I clinical trial.
Ann Surg.
1997;
225
484-491
(5)
MissingFormLabel
- 63
Werner A, Duvar S, Muthing J, Buntemeyer H, Kahmann U, Lunsdorf H, Lehmann J.
Cultivation and characterization of a new immortalized human hepatocyte cell line,
HepZ, for use in an artificial liver support system.
Ann N Y Acad Sci.
1999;
875
364-368
MissingFormLabel
- 64
Yoon J H, Lee H V, Lee J S, Park J B, Kim C Y.
Development of a non-transformed human liver cell line with differentiated-hepatocyte
and urea-synthetic functions: applicable for bioartificial liver.
Int J Artif Organs.
1999;
22
769-77
(11)
MissingFormLabel
- 65
Glicklis R, Shapiro L, Agbaria R, Merchuk J C, Cohen S.
Hepatocyte behavior within three-dimensional porous alginate scaffolds.
Biotechnol Bioeng.
2000;
67
344-353
(3)
MissingFormLabel
- 66
Selden C, Shariat A, McCloskey P, Ryder T, Roberts E, Hodgson H.
Three-dimensional in vitro cell culture leads to a marked upregulation of cell function
in human hepatocyte cell lines-an important tool for the development of a bioartificial
liver machine.
Ann N Y Acad Sci.
1999;
875
353-363
MissingFormLabel
- 67
Qiang S, Yaoting Y, Hongyin L, Klinkmann H.
Comparative evaluation of different membrane for the construction of an artificial
liver support system.
Int J Artif Organs.
1997;
20
119-124
(2)
MissingFormLabel
- 68
Foley D P, Collins B R, Magee J C, Platt J L, Katz E, Harland R C, Meyers W C, Chari R S.
Bile acids in xenogeneic ex-vivo liver perfusion: function of xenoperfused livers
and compatibility with human bile salts and porcine livers.
Transplantation.
2000;
69
242-248
(2)
MissingFormLabel
- 69
Iwata H, Sajiki T, Maeda H, Park Y G, Zhu B, Satoh S, Uesugi T, Ikai I, Yamaoka Y, Ikada Y.
In vitro evaluation of metabolic functions of a bioartificial liver.
ASAIO J.
1999;
45
299-306
(4)
MissingFormLabel
- 70
Tacke S J, Kurth R, Denner J.
Porcine endogenous retroviruses inhibit human immune cell function: risk for xenotransplantation?.
Virology.
2000;
268
87-93
(1)
MissingFormLabel
- 71
Nyberg S L, Hibbs J R, Hardin J A, Germer J J, Platt J L, Paya C V, Wiesner R H.
Influence of Human Fulminant Hepatic Failure Sera on Endogenous Retroviral Expression
in Pig Hepatocytes.
Liver Transpl.
2000;
6
76-84
(1)
MissingFormLabel
- 72
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
829-833
(9)
MissingFormLabel
- 73
Hammer C.
Xenotransplantation: facts and fiction.
Ann Chir Gynaecol.
1997;
86
195-201
(2)
MissingFormLabel
- 74
Hammer C.
Physiological obstacles after xenotransplantation.
Ann N Y Acad Sci.
1998;
862
19-27
MissingFormLabel
- 75
Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, Degott C, Bezeaud A, Rueff B, Benhamou J P.
Multivariate analysis of prognostic factors in fulminant hepatitis B.
Hepatology.
1986;
6
648-651
(4)
MissingFormLabel
- 76
O’Grady J G, Alexander G J, Hayllar K M, Williams R.
Early indicators of prognosis in fulminant hepatic failure.
Gastroenterology.
1989;
97
439-445
(2)
MissingFormLabel
- 77
Shakil A O, Kramer D, Mazariegos G V, Fung J J, Rakela J.
Acute liver failure: clinical features, outcome analysis, and predicability of prognostic
criteria.
Liver Transpl.
2000;
6
163-169
(2)
MissingFormLabel
- 78
Stockman H, Hiemstra C, Marquet R, Ijzermans J.
Extracorporeal perfusion for the treatment of acute liver failure.
Ann Surg.
2000;
231
460-470
MissingFormLabel
Address of author to whom requests for reprints should be sent
Mustapha Adham, MD, PhD
Department of General, Digestive Surgery and Liver Transplantation
Croix Rousse Hospital,
103, gde rue de la Croix Rousse,
69317 Lyon, France
Phone: +33 (0) 472-071-632
Phone: Secretariat : +33 (0) 472-071-032
Fax: +33 (0) 472-071-897
Email: mustapha.adham@chu-lyon.fr