Proceedings of the 6th International Conference on CRRT
Acute-on-Chronic Liver Failure: Pathophysiological Basis of Therapeutic OptionsJalan R. · Williams R.
Institute of Hepatology, University College, London Medical School and UCL Hospitals, London, UK
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
The vast majority of patients that are referred to a specialist hepatological centre suffer from acute deterioration of their chronic liver disease. Yet, this entity of acute-on-chronic liver failure remains poorly defined. With the emergence of newer liver support strategies, it has become necessary to define this entity, its pathophysiology and the short- and long-term prognosis. This review focusses upon how a precipitant such as an episode of gastrointestinal bleeding or sepsis may start a cascade of events that culminate in end-organ dysfunction and liver failure. We briefly review the pathophysiological basis of the therapeutic modalities that are available. Our current strategy for the management of liver failure involves supportive therapy for the end-organs with the hope that liver function would recover if sufficient time for such a recovery is allowed. Because liver failure, whether of the acute or acute-on-chronic variety, is potentially reversible, the stage is set for the application of newer liver-support strategies to enhance the recovery process.
© 2002 S. Karger AG, Basel
- Zimmerman JE, Wagner DP, Seneff MG, Becker RB, Sun X, Knaus WA: Intensive care unit admissions with cirrhosis: Risk-stratifying patient groups and predicting individual survival. Hepatology 1996;23:1393–1401.
- de Mendonca A, Vincent JL, Suter PM, Moreno R, Dearden NM, Antonelli M, Takala J, Sprung C, Cantraine F: Acute renal failure in the ICU: Risk factors and outcome evaluated by the SOFA score. Intensive Care Med 2000;26:915–921.
- Grace ND: Prevention of initial variceal hemorrhage. Gastroenterol Clin North Am 1992;21:149–161.
- Teran JC, Imperiale TF, Mullen KD, Tavill AS, McCullough AJ: Primary prophylaxis of variceal bleeding in cirrhosis: A cost-effectiveness analysis. Gastroenterology 1997;112:473–482.
- Garden OJ, Motyl H, Gilmour WH, Utley RJ, Carter DC: Prediction of outcome following acute variceal haemorrhage. Br J Surg 1985;72:91–95.
- Pauwels A, Mostefa-Kara N, Debenes B, Degoutte E, Lévy VG: Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection. Hepatology 1996;24:802–806.
- Bleichner G, Boulanger R, Squara P, Sollet JP, Parent A: Frequency of infections in cirrhotic patients presenting with acute gastrointestinal haemorrhage. Br J Surg 1986;73:724–726.
Bessman AN, Hawkins R: The relative effects of enterically administered plasma and packed cells on circulating blood ammonia. Gastroenterology 1963;45:368–373.
- van Berlo CLH, van de Boogaard AEJM, van der Heijden MAH, van Eijk HMH, Janssen MA, Bost MCF, Soeters PB: Is increased ammonia liberation after bleeding in the digestive tract the consequence of complete absence of isoleucine in hemoglobin? A study in pigs. Hepatology 1989;10:315–323.
Hill RJ, Konigsberg W: The structure of human hemoglobin. J Biol Chem 1962;237:3151–3156.
- Lawn RM, Efstratiadis A, O’Connell C, Maniatis T: The nucleotide sequence of the human beta-globin gene. Cell 1980;21:647–651.
- Harper AE, Miller RH, Block KP: Branched-chain amino acid metabolism. Annu Rev Nutr 1984;4:409–454.
- Dejong CHC, Meijerink WJHJ, van Berlo CLH, Deutz NEP, Soeters PB: Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans. Gut 1996;39:13–17.
- Olde Damink SWM, Dejong CHC, Deutz NEP, Soeters PB: Decreased plasma and tissue isoleucine levels after simulated gastrointestinal bleeding by blood gavages in chronic portacaval shunted rats. Gut 1997;40:418–424.
- Kohn A: Differential effects of isoleucine deprivation on cell motility, membrane transport and DNA synthesis in NIL8 hamster cells. Exp Cell Res 1975;94:15–22.
- Tobey RA, Ley KD: Isoleucine-mediated regulation of genome replication in various mammalian cell lines. Cancer Res 1971;31:46–51.
- Deutz NEP, Reijven PLM, Bost MCF, van Berlo CLH, Soeters PB: Modification of the effects of blood on amino acid metabolism by intravenous isoleucine. Gastroenterology 1991;101:1613–1620.
- Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T: Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: A meta-analysis. Hepatology 1999;29:1655–1661.
- Grange JD, Roulot D, Pelletier G, Pariente EA, Denis J, Ink O, Blanc P, Richardet JP, Vinel JP, Delisle F, Fischer D, Flahault A, Amiot X: Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: A double-blind randomized trial. J Hepatol 1998;29:430–436.
- Takada Y, Ishiguro S, Fukunaga K, Gu M, Tanugichi H, Seino K, et al: Increased intracranial pressure in a porcine model of fulminant hepatic failure using amatoxin and endotoxin. J Hepatol 2001;34:825–830.
- 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.
- Dirix LY, Polson RJ, Richardson A, Williams R: Primary sepsis presenting as fulminant hepatic failure. Q J Med 1989;73:1037–1043.
- Galanos C, Freudenberg MA, Reutter W: Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci USA 1979;76:5939–5943.
- Czaja MJ, Xu J, Ju Y, Alt E, Schmiedeberg P: Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. Hepatology 1994;19:1282–1289.
- Leist M, Gantner F, Naumann H, Bluethmann H, Vogt K, Brigelius-Flohe R, Nicotera P, Volk HD, Wendel A: Tumor necrosis factor-induced apoptosis during the poisoning of mice with hepatotoxins. Gastroenterology 1997;112:923–934.
Bosch J, Garcia-Pagan JC: Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000;32(suppl 1):141–156.
Newby DE, Jalan R, Masumoto S, et al: Peripheral vascular tone in patients with cirrhosis: Role of the renin-angiotensin and sympathetic nervous systems. Cardiovasc-Res 1998;38:221–228.
- Laszlo F, Whittle BJ, Evans SM, Moncada S: Association of microvascular leakage with induction of nitric oxide synthase: Effects of nitric oxide synthase inhibitors in various organs. Eur J Pharmacol 1995;283:47–53.
- Helmy A, Jalan R, Newby DE, Johnston NR, Hayes PC, Webb DJ: Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis. Hepatology 2001;33:826–831.
Vallance P, Collier J, Moncada S: Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989;ii:997–1000.
Boughton-Smith NK, Evans SM, Laszlo F, Whittle BJ, Moncada S: The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Phamacol 1993;110:1189–1195.
- Mitchell JA, Kohlhaas KL, Sorrentino R, Warner TD, Murad F, Vane JR: Induction by endotoxin of nitric oxide synthase in the rat mesentery: Lack of effect on action of vasoconstrictors. Br J Pharmacol 1993;109:265–270.
- Salter M, Knowles RG, Moncada S: Widespread tissue distribution, species distribution and changes in activity of Ca[2+]-dependent and Ca[2+]-independent nitric oxide synthases. FEBS Lett 1991;291:145–149.
- Meyer J, Lentz CW, Stothert JC Jr, Traber LD, Herndon DN, Traber DL: Effects of nitric oxide synthesis inhibition in hyperdynamic endotoxemia. Crit Care Med 1994;22:306–312.
- Wong F, Sniderman K, Blendis L: The renal sympathetic and renin-angiotensin response to lower body negative pressure in well-compensated cirrhosis. Gastroenterology 1998;115:397–405.
- Niederberger M, Gines P, Martin PY, Tsai P, Morris K, McMurtry I, Schrier RW: Comparison of vascular nitric oxide production on systemic hemodynamics in cirrhosis versus prehepatic portal hypertension in rats. Hepatology 1996;24:947–951.
- Martin PY, Ohara M, Gines P, Xu DL, St John J, Niederberger M, Schrier RW: Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. J Clin Invest 1998;101:235–242.
- Cunha FQ, Assreuy J, Moss DW, Rees D, Leal LM, Moncada S, Carrier M, O’Donnell CA, Liew FY: Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: Role of TNF-alpha and IL-1-beta. Immunology 1994;81:211–215.
- MacNaul KL, Hutchinson NI: Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions. Biochem Biophys Res Commun 1993;196:1330–1334.
- Annane D, Sanquer S, Sebille V, Faye A, Djuranovic D, Raphael JC, Gajdos P, Bellissant E: Compartmentalised inducible nitric-oxide synthase activity in septic shock. Lancet 2000;355:1143–1148.
- Epstein M, Larios O, Johnson G: Effects of water immersion on plasma catecholamines in decompensated cirrhosis. Implications for deranged sodium and water homeostasis. Miner Electrolyte Metab 1985;11:25–34.
- Henriksen JH, Ring-Larsen H: Hepatorenal disorders: Role of the sympathetic nervous system. Semin Liver Dis 1994;14:35–43.
- Lang F, Tschernko E, Schulze E, Ottl I, Ritter M, Volkl H, Hallbrucker C, Haussinger D: Hepatorenal reflex regulating kidney function. Hepatology 1991;14:590–594.
- Moore K, Ward P, Taylor G, Williams R: Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome. Gastroenterology 1991;100:1069–1077.
- Gines A, Escorell A, Gines P, Salo J, Jimenez W, Inglada L, Navasa M, Claria J, Rimola A, Arroyo V, Rodes J: Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology 1993;105:229–236.
- Persson PB, Ehmke H, Kircheim HR: Sympathetic modulation of renal autoregulation by carotid occlusion in conscious dogs. Am J Physiol 1990;258:F364–F370.
Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D, Erlinger S, Lebrec D: Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. Hepatology 1998;29:565–570.
- Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, Amodio P, Sticca A, Caregaro L, Maffei-Faccioli A, Gatta A: Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999;29:1690–1697.
- Gülberg V, Bilzer M, Gerbes AL: Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine. Hepatology 1999;30:870–875.
Holt S, Goodier D, Marley R, Patch D, Burroughs A, Fernando B, Harry D, Moore K: Improvement in renal function in hepatorenal syndrome with N-acetylcysteine Lancet 1999;353:294–295.
- Brensing KA, Textor J, Strunk H, Klehr HU, Schild H, Sauerbruch T: Transjugular intrahepatic portosystemic stent-shunt for hepatorenal syndrome. Lancet 1997;349:697–698.
Guevara M, Gines P, Fernandez-Esparrach G, Sort P, Salmeron JM, Jimenez W, Arroyo V, Rodes J: Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology 1998;29:35–41.
- Gonwa TA, Morris CA, Goldstein RM, Husberg BS, Klintmalm GB: Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome – Experience in 300 patients. Transplantation 1991;51:428–430.
Conn HO, Lieberthal MM: The Hepatic Coma Syndromes and Lactulose. Baltimore, Williams & Wilkins, 1979.
- Mans AM, Biebuyck JF, Shelley K, Hawkins RA: Regional blood brain barrier permeability to amino acids after portacaval anastomosis. J Neurochem 1982;38:705–713.
- Kreis R, Farrow N, Ross BD: Localized 1H NMR spectroscopy in patients with chronic hepatic encephalopathy. Analysis of changes in cerebral glutamine, choline and inositols. NMR Biomed 1991;4:109–116.
- Lockwood AH, Yap EWH, Wong WH: Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephaloapthy. J Cereb Blood Flow Metab 1991;11:337–341.
- O’Carrol RE, Hayes PC, Ebemeir KP, Dougall N, Murray C, Best JJK, Bouchier IAD, Goodwin GM: Regional cerebral blood flow and cognitive function in patients with chronic liver disease. Lancet 1991;337:1250–1253.
- Hindfelt B, Plum F, Duffy TE: Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest 1977;59:386–396.
- Basile AS, Jones EA, Skolnick P: The pathogenesis and treatment of hepatic encephalopathy: Evidence for the involvement of benzodiazepine receptor ligands. Pharmacol Rev 1991;43:27–71.
Stahl J: Studies of the blood ammonia in liver disease. Its diagnostic, prognostic and therapeutic significance. Ann Intern Med 1963;58:1–24.
- Basile AS, Jones EA: Ammonia and GABAergic neurotransmission: Interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology 1997;25:1303–1305.
Laubenberger J, Haussinger D, Bayer S, Gufler H, Kennig J, Langer M: Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology 1996;112:1610–1616.
- Soeters PB, Weir JC, Ebeid AM, Fischer JE: Insulin, glucagon, portasystemic shunting and hepatic failure in dogs. J Surg Res 1977;23:183–188.
Pomier-Layrargues G, Shapcott D, Spahr L, Butterworth RF: Accumulation of manganese and copper in the pallidum of cirrhotic patients: Role in the pathogenesis of hepatic encephalopathy? Metab Brain Dis 1995;10:351–354.
- Spahr L, Butterworth RF, Fontaine S, Bui L, Therrien G, Milette PC, Lebrun LH, Zayed J, Leblanc A, Pomier-Layrargeus G: Increased blood manganese in cirrhotic patients: Relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996;24:1116–1120.
- Butterworth RF: A disorder of multiple neurotransmitter systems. Adv Exp Med Biol 1994;368:79–88.
- Michalak A, Rose C, Butterworth J, Butterworth RF: Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure. Hepatology 1996;24:908–913.
- Jones EA, Gammal SH, Martin P: Hepatic encephalopathy: New light on an old problem. Q J Med 1988;69:851–867.
- Mullen KD, Jones EA: Natural benzodiazepines and hepatic encephalopathy. Semin Liver Dis 1996;16:255–264.
- Jalan R, Turjanski N, Taylor-Robinson SD, Koepp MJ, Richardson MP, Wilson JA, Bell JD, Brooks DJ: Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis. Gut 2000;46:546–552.
- Itzhak Y, RoigCantisano A, Dombro RS, Norenberg MD: Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain. Brain Res 1995;705:345–348.
- Baraldi M, Zeneroli ML, Ricci P, Ventura E: Downregulation of striatal dopamine receptors in experimental hepatic encephalopathy. Life Sci 1983;32:1417–1425.
Fischer JE, Baldessarini RJ: False neurotransmitters and hepatic failure. Lancet 1971;ii:75–80.
- Ferenci P, Herneth A, Steindl P: Newer approaches to therapy of hepatic encephalopathy. Semin Liver Dis 1996;16:329–338.
- Simmons F, Goldstein H, Boyle J: A controlled clinical trial of lactulose in hepatic encephalopathy. Gastroenterology 1970;59:827–832.
- Morgan MY, Hawley KE: Lactitol vs. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: A double-blind, randomized trial. Hepatology 1987;7:1278–1284.
- Sushma S, Dasarathy S, Tanden RK, Jain S, Gupta S, Bhist MS: Sodium benzoate in the treatment of acute hepatic encephalopathy: A double-blind randomised trial. Hepatology 1992;16:138–144.
- Kircheis G, Nilius R, Held C, Berndt H, Buvhner M, Gortelmeyer R, Hendricks R, Kruger B, Kuklinski B, Meister H, Otto HJ, Rink C, Rosch W, Stauch S: Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study. Hepatology 1997;25:1351–1360.
Fischer JE: Branched chain enriched amino acid solutions in patients with liver failure: An early example of nutritional pharmacology. JPEN J Parenter Enteral Nutr 1990;14(suppl 5):249S–256S.
- Ellis AJ, Hughes RD, Wendon JA, Dunne J, Langley PG, Kelly JH, Gislason GT, Sussman NL, Williams R: Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology 1996;24:1446–1451.
- Detry O, Arkadopoulos N, Ting P, Kahaku E, Watanabe FD, Rozga J, Demetriou AA: Clinical use of a bioartificial liver in the treatment of acetaminophen-induced fulminant hepatic failure. Am Surg 1999;65:934–938.
- Flendrig LM, Calise F, Di Florio E, Mancini A, Ceriello A, Santaniello W, Mezza E, Sicoli F, Belleza G, Bracco A, Cozzolino S, Scala D, Mazzone M, Fattore M, Gonzales E, Chamuleau RA: Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver. Int J Artif Organs 1999;22:701–709.
- Busse B, Gerlach JC: Bioreactors for hybrid liver support: Historical aspects and novel designs. Ann NY Acad Sci 1999;875:326–339.
- Weiss RA: Xenografts and retroviruses. Science 1999;285:1221–1222.
- 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;94:1186–1192.
- Ash SR, Steczko J, Knab WR, Blake DE, Carr DJ, Harker KD, Levy H: Push-pull sorbent-based pheresis and hemodiabsorption in the treatment of hepatic failure: Preliminary results of a clinical trial with the BioLogic-DTPF System. Ther Apher 2000;4:218–228.
- 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;23:319–330.
- 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:M621–M625.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.