Therapiemöglichkeiten beim Leberversagen

Zusammenfassung

Trotz verbesserter Kenntnisse lässt sich ein Leberversagen im Rahmen von Leberteilresektionen nicht immer verhindern. In diesen Situationen sind die Therapiemöglichkeiten begrenzt. Neben klassischen konservativen Verfahren, werden in letzter Zeit zunehmend Leberersatzverfahren angewendet und verbessert.

Im Wesentlichen können drei Gruppen von Verfahren unterschieden werden: Ein der Dialyse ähnliches physikalisches Verfahren, das bereits ca. 10 000-mal zum Einsatz kam, dessen Stellenwerte in der Behandlung des Leberversagens jedoch noch zu untermauern ist. Ein weiteres Verfahren basiert auf hybrider Leberunterstützung, wobei isolierte Hepatozyten extrakorporal eine Entgiftung gewährleisten sollen. Schließlich die extrakorporale Leberperfusion, die den Vorteil einer Galleexkretion erbringen kann.

Wegen der hohen Regenerationskapazität der Leber würden diese Leberersatzverfahren nur für eine beschränkte Zeit benötigt werden.

Abstract

There has been tremendous improvement in the past concerning the prevention of liver failure after liver resections. Still this can not be achieved in all cases. Treatment options are still quite limited. Besides classical conservative treatment, liver assist devices are being investigated.

Mainly three different approaches can be distinguished. First, a physical system, similar to dialysis, but with the addition of albumin, enabling clearance of albumin bound compounds. Second, a system using isolated hepatocytes, which shall lead to detoxification and ideally to some extend of liver synthesis. Finally, extracorporeal perfusion of whole livers is carried out, which potentially has the advantage of producing bile and thereby clearing toxic substances.

As the liver has great potential to regenerate such systems would probably only be required for a limited time period.

Schlüsselwörter

Leberversagen - Leberteilresektion - Leberersatzverfahren - MARS - Hybride Leberunterstützungssysteme - Extrakorporale Leberperfusion

Key words

Liver failure - liver resection - liver assist device - MARS - bioreactor - extracorporeal liver perfusion

Literatur

• 1 Abouna G M. Experience with extracorporeal pig liver perfusion in the treatment of hepatic coma.  Gut. 1968;  9 730-731
• 2 Baudouin S V, Howdle P, O'Grady J G, Webster N R. Acute lung injury in fulminant hepatic failure following paracetamol poisoning.  Thorax. 1995;  50 399-402
• 3 Bernal W. Intensive care support therapy.  Liver Transpl. 2003;  9 S 15-S 17
• 4 Bismuth H, Houssin D, Ornowski J, Meriggi F. Liver resections in cirrhotic patients: a Western experience.  World J Surg. 1986;  10 311-317
• 5 Blei A T. Pathophysiology of brain edema in fulminant hepatic failure, revisited 13.  Metab Brain Dis. 2001;  16 85-94
• 6 Butterworth R F. Pathophysiology of hepatic encephalopathy: a new look at ammonia.  Metab Brain Dis. 2002;  17 221-227
• 7 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. Treatment of hepatic failure with ex vivo pig- liver perfusion followed by liver transplantation.  N Engl J Med. 1994;  331 234-237
• 8 Demetriou A A, Whiting J, Levenson S M, Chowdhury N R, Schechner R, Michalski S, Feldman D, Chowdhury J R. New method of hepatocyte transplantation and extracorporeal liver support.  Ann Surg. 1986;  204 259-271
• 9 Eiseman B, Kawamura T, Tate I, Velasquez A. Effect of external pressure on oxygen utilization by the liver.  Ann Surg. 1970;  171 211-218
• 10 Eiseman B, Liem D S, Raffucci F. Heterologous liver perfusion in treatment of hepatic failure.  Ann Surg. 1965;  162 329-345
• 11 Fan S T, Lo C M, Liu C L, Lam C M, Yuen W K, Yeung C, Wong J. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.  Ann Surg. 1999;  229 322-330
• 12 Filipponi F, Fabbri L P, Marsili M, Falcini F, Benassai C, Nucera- M, Romagnoli P. A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury.  Eur Surg Res. 1991;  23 58-64
• 13 Fong Y, Cohen A M, Fortner J G, Enker W E, Turnbull A D, Coit D G, Marrero A M, Prasad M, Blumgart L H, Brennan M F. Liver resection for colorectal metastases.  J Clin Oncol. 1997;  15 938-946
• 14 Fox I J, Langnas A N, Fristoe L W, Shaefer M S, Vogel J E, Antonson D, 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
• 15 Gerlach J C, Schnoy N, Encke J, Smith M D, Müller C, Neuhaus P. Improved hepatocyte in vitro maintenance in a culture model with woven multicompartment capillary systems: electron microscopy studies.  Hepatology. 1995;  22 546-552
• 16 Gozzetti G, Mazziotti A, Cavallari A, Bellusci R, Bolondi L, Grigioni W, Bragaglia R, Grazi G L, De Raffele E. Clinical experience with hepatic resections for hepatocellular carcinoma in patients with cirrhosis.  Surg Gynecol Obstet. 1988;  166 503-510
• 17 Hanid M A, Davies M, Mellon P J, Silk D B, Strunin L, McCabe J J, Williams R. Clinical monitoring of intracranial pressure in fulminant hepatic failure.  Gut. 1980;  21 866-869
• 18 Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M, Klammt S, Loehr M, Liebe S, Mitzner S, Schmidt R, Stange J. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.  Hepatology. 2002;  36 949-958
• 19 Jalan R, Olde Damink S W, Deutz N E, Hayes P C, Lee A. Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia.  Hepatology. 2001;  34 50-54
• 20 Jarnagin W R, Gonen M, Fong Y, DeMatteo R P, Ben Porat L, Little S, Corvera C, Weber S, Blumgart L H. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade.  Ann Surg. 2002;  236 397-406
• 21 Jauregui H O, Naik S, Solomon B A, Duffy R L, Lipsky M H, Galletti P M. Attachment of adult rat hepatocytes to modified Amicon XM-50 membranes.  Trans Am Soc Artif Intern Organs. 1983;  29 698-703
• 22 Kelly J H, Koussayer T, He D E, Chong M G, Shang T A, Whisennand H H, Sussman N L. An improved model of acetaminophen-induced fulminant hepatic failure in dogs.  Hepatology. 1992;  15 329-335
• 23 Knazek R A, Gullino P M, Kohler P O, Dedrick R L. Cell culture on artificial capillaries: an approach to tissue growth in vitro.  Science. 1972;  178 65-66
• 24 Larsen F S. Cerebral circulation in liver failure: Ohm's law in force.  Semin Liver Dis. 1996;  16 281-292
• 25 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;  27 272-280
• 26 Margulis M S, Erukhimov E A, Andreiman L A, Kuznetsov K A, Viksna L M, Kuznetsov A I, Deviatov V V. Primenenie gemoperfuzii cherez vzves' kriokonservirovannykh gepatotsitov pri ostroi pechenochnoi nedostatochnosti. [The use of hemoperfusion through a suspension of cryopreserved hepatocytes in acute liver failure].  Vestn Khir Im I I Grek. 1992;  148 83-87
• 27 Margulis M S, Erukhimov E A, Andreiman L A, Viksna L M. 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
• 28 Matsumura K N, Guevara G R, Huston H, Hamilton W L, Rikimaru M, Yamasaki G, Matsumura M S. Hybrid bioartificial liver in hepatic failure: preliminary clinical report.  Surgery. 1987;  101 99-103
• 29 Mitzner S, Williams R. Albumin dialysis MARS 2003: what evidence, how to proceed?.  Liver Int. 2003;  23 (Suppl 3) 3-4
• 30 Miwa Y, Kato M, Moriwaki H, Okuno M, Sugihara J, Ohnishi H, Yoshida T, Muto Y, Nakayama M, Morioka Y. et al . Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure.  Hepatology. 1995;  22 291-296
• 31 Neuhaus P, Blumhardt G. Extracorporeal liver perfusion: applications of an improved model for experimental studies of the liver.  Int J Artif Organs. 1993;  16 729-739
• 32 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
• 33 Nyberg S L, Shatford R A, Hu W S, Payne W D, Cerra F B. Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).  Crit Care Med. 1992;  20 1157-1168
• 34 Rolando N, Philpott H J, Williams R. Bacterial and fungal infection in acute liver failure.  Semin Liver Dis. 1996;  16 389-402
• 35 Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure.  Hepatology. 2000;  32 734-739
• 36 Rozga J, Holzman M D, Ro M S, Griffin D W, Neuzil D F, Giorgio T, Moscioni A D, Demetriou A A. Development of a hybrid bioartificial liver.  Ann Surg. 1993;  217 502-509
• 37 Schön M R, Gerlach J C, Neuhaus P. Perspektiven der xenogenen Lebertransplantation. In: Grimm H (ed). Xenotransplantation. Schattauer, Stuttgart 2003; 369-384
• 38 Schön M R, Kollmar O, Wolf S, Schrem H, Matthes M, Akkoc N, Schnoy N C, Neuhaus P. Liver transplantation after organ preservation with normothermic extracorporeal perfusion.  Ann Surg. 2001;  233 114-123
• 39 Schön M R, Puhl G, Frank J, Neuhaus P. Hemodialysis improves results of pig liver perfusion after warm ischemic injury.  Transplant Proc. 1993;  25 3239-3243
• 40 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
• 41 Sussman N L, Chong M G, Koussayer T, He D E, Shang T A, Whisennand H, Kelly J H. Reversal of fulminant hepatic failure using an extracorporeal liver assist device.  Hepatology. 1992;  16 60-65
• 42 Sussman N L, Kelly J H. Improved liver function following treatment with an extracorporeal liver assist device.  Artif Organs. 1993;  17 27-30
• 43 Takabatake H, Koide N, Tsuji T. Encapsulated multicellular spheroids of rat hepatocytes produce albumin and urea in a spouted bed circulating culture system.  Artif Organs. 1991;  15 474-480
• 44 Takano S, Oishi H, Kono S, Kawakami S, Nakamura M, Kubota N, Iwai S. Retrospective analysis of type of hepatic resection for hepatocellular carcinoma.  Br J Surg. 2000;  87 65-70
• 45 Te Velde A A, Ladiges N C, Flendrig L M, Chamuleau R A. Functional activity of isolated pig hepatocytes attached to different extracellular matrix substrates. Implication for application of pig hepatocytes in a bioartificial liver.  J Hepatol. 1995;  23 184-192
• 46 Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, Kubota K, Zucchi A. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach.  Arch Surg. 1999;  134 984-992
• 47 Tromm A, Griga T, Greving I, Hilden H, Huppe D, Schwegler U, Micklefield G H, May B. Orthograde whole gut irrigation with mannite versus paromomycine + lactulose as prophylaxis of hepatic encephalopathy in patients with cirrhosis and upper gastrointestinal bleeding: results of a controlled randomized trial.  Hepatogastroenterology. 2000;  47 473-477
• 48 Tung L C, Häring R, Waldschmidt J, Weber D. Erfahrungen mit der extrakorporalen Leberperfusion bei akutem Leberversagen.  Zentralbl Chir. 1980;  105 1195-1205
• 49 Uchino J, Tsuburaya T, Kumagai F, Hase T, Hamada T, Komai T, Funatsu A, Hashimura E, Nakamura K, Kon T. A hybrid bioartificial liver composed of multiplated hepatocyte monolayers.  ASAIO Trans. 1988;  34 972-977
• 50 Velasquez A, Hill L, Novak V, Eiseman B. Improved extracorporeal hepatic assist using intermittent external pressure on the liver.  Am Surg. 1970;  36 657-661
• 51 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;  225 484-494
• 52 Wei A C, Tung-Ping P R, Fan S T, Wong J. Risk factors for perioperative morbidity and mortality after extended hepatectomy for hepatocellular carcinoma.  Br J Surg. 2003;  90 33-41
• 53 Wettstein M, Haussinger D. [Hepatic encephalopathy-therapy].  Dtsch Med Wochenschr. 2003;  128 2658-2660
• 54 Winney R J, Kean D M, Best J J, Smith M A. Changes in brain water with haemodialysis.  Lancet. 1986;  2 1107-1108
• 55 Wu C C, Yeh D C, Lin M C, Liu T J, P'eng F K. Improving operative safety for cirrhotic liver resection.  Br J Surg. 2001;  88 210-215
• 56 Yanagi K, Ookawa K, Mizuno S, Ohshima N. Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel.  ASAIO Trans. 1989;  35 570-572