Acute-on-Chronic Liver Failure in Cirrhosis: Defining and Managing Organ Dysfunction

  • D. Shawcross
  • J. Wendon


The term ‘acute-on-chronic liver failure’ was first used in the 1960s mainly in relation to flares of viral hepatitis. It was not until the turn of the millennium, however, that the term entered the everyday vocabulary of hepatologists when it was used to describe the pathophysiological deterioration in patients with cirrhosis mainly in the context of trials utilizing liver support devices [1]. Since then, a consensus definition of acute-on-chronic liver failure has been fiercely debated. The terms ‘compensated’ and ‘decompensated’ liver disease are rarely used in the critical care arena with patients being defined with regard to the degree of organ dysfunction rather than by quantifying liver synthetic function per se. Moreover, it has been shown that the prognosis in patients with cirrhosis is strongly correlated with the number of failing organs [2, 3, 4] and that certain cohorts of patients with severe hepatic encephalopathy, acute variceal bleeding, and organ failure benefit from admission to a critical care environment [5].


Liver Failure Portal Hypertension Hepatic Encephalopathy Systemic Inflammatory Response Syndrome Sequential Organ Failure Assessment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sen S, Davies NA, Mookerjee RP, et al (2004) Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl 10: 1109–1119CrossRefPubMedGoogle Scholar
  2. 2.
    Gildea TR, Cook WC, Nelson DR, et al (2004) Predictors of long-term mortality in patients with cirrhosis of the liver admitted to a medical ICU. Chest 126: 1598–1603CrossRefPubMedGoogle Scholar
  3. 3.
    Cholongitas E, Senzolo M, Patch D, et al (2006) Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. Aliment Pharmacol Ther 23: 883–893CrossRefPubMedGoogle Scholar
  4. 4.
    Zimmerman JE, Wagner DP, Seneff MG, Becker RB, Sun X, Knaus WA (1996) Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival. Hepatology 23: 1393–1401CrossRefPubMedGoogle Scholar
  5. 5.
    Shawcross D, Austin M, Abeles R, et al (2008) Defining the impact of organ dysfunction in cirrhosis: survival at a cost? Gut 57 (Suppl 1):A12–A13 (abst)Google Scholar
  6. 6.
    Levy M, Fink M, Marshall J, et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29: 530–538PubMedGoogle Scholar
  7. 7.
    Rivers E, Nguyen B, Havastad S, et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345: 1368–1377CrossRefPubMedGoogle Scholar
  8. 8.
    Knaus W, Draper E, Wagner D, Zimmerman J (1985) Prognosis in acute organ-system failure. Ann Surg 202: 685–693CrossRefPubMedGoogle Scholar
  9. 9.
    Vincent JL, Moreno R, Takala J, et al (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22: 707–710CrossRefPubMedGoogle Scholar
  10. 10.
    Austin M, Shawcross D (2008) Outcome of patients with cirrhosis admitted to intensive care. Curr Opin Crit Care 14: 202–207CrossRefPubMedGoogle Scholar
  11. 11.
    Pugh R, Murray-Lyon I, Dawson J, Pietroni M, Williams R (1973) Transection of the oesophagus for bleeding oesphageal varices. Br J Surg 60: 646–649CrossRefPubMedGoogle Scholar
  12. 12.
    Kamath K, Weisner R, Malinchoc M, et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33: 464–470CrossRefPubMedGoogle Scholar
  13. 13.
    Jenq C, Tsai M, Tain Y, et al (2007) RIFLE classification can predict short-term prognosis in critically ill cirrhotic patients. Intensive Care Med 33: 1921–1930CrossRefPubMedGoogle Scholar
  14. 14.
    Wasmuth H, Kunz D, Yagmur E, et al (2005) Patients with acute on chronic liver failure display’ sepsis-like’ immune paralysis. J Hepatol 42: 195–201CrossRefPubMedGoogle Scholar
  15. 15.
    Wong F, Bernardi M, Balk R, et al (2005) Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut 54: 718–725CrossRefPubMedGoogle Scholar
  16. 16.
    Antoniades CG, Berry PA, Davies ET, et al (2006) Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure. Hepatology 44: 34–43CrossRefPubMedGoogle Scholar
  17. 17.
    Jalan R, Newby DE, Damink SW, Redhead DN, Hayes PC, Lee A (2001) Acute changes in cerebral blood flow and metabolism during portasystemic shunting. Liver Transpl 7: 274–278CrossRefPubMedGoogle Scholar
  18. 18.
    Van der Linden P, Le Moine O, Ghysels M, Ortinez M, Deviere J (1996) Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function. Hepatology 23: 982–987CrossRefPubMedGoogle Scholar
  19. 19.
    Harry R, Auzinger G, Wendon J (2002) The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology 36: 395–402CrossRefPubMedGoogle Scholar
  20. 20.
    Marik P, Gayowski T, Starzl T (2005) The hepatoadrenal syndrome: a common yet unrecognised clinical condition. Crit Care Med 33: 1254–1259CrossRefPubMedGoogle Scholar
  21. 21.
    Fernandez J, Escorsell A, Zabalza M, et al (2006) Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival. Hepatology 44: 1288–1295CrossRefPubMedGoogle Scholar
  22. 22.
    Ferenci P, Lockwood A, Mullen K, et al (2002) Hepatic Encephalopathy — Definition, nomenclature, diagnosis and quantification: Final report of the Working Party at the 11th World Congress of Gastroenterology, Vienna, 1998. Hepatology 35: 716–721CrossRefPubMedGoogle Scholar
  23. 23.
    Cordoba J, Alonso J, Rovira A, et al (2001) The development of low-grade cerebral oedema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation. J Hepatol 35: 598–604CrossRefPubMedGoogle Scholar
  24. 24.
    Als-Nielsen B, Gluud L, Gluud C (2004)Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ 328: 1046–1050CrossRefPubMedGoogle Scholar
  25. 25.
    Cordoba J, Lopez-Hellin J, Planas M, et al (2004) Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol 41: 38–43CrossRefPubMedGoogle Scholar
  26. 26.
    Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32: 734–739CrossRefPubMedGoogle Scholar
  27. 27.
    Shawcross D, Davies N, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40: 247–254CrossRefPubMedGoogle Scholar
  28. 28.
    Liu Q, Duan ZP, Ha dK, Bengmark S, Kurtovic J, Riordan SM (2004) Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 39: 1441–1449CrossRefPubMedGoogle Scholar
  29. 29.
    Hassanein T, Tofteng F, Brown R, et al (2007) Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 46: 1853–1862CrossRefPubMedGoogle Scholar
  30. 30.
    Bernal W, Auzinger G, Sizer E, Wendon J (2008) Intensive care management for acute liver failure. Semin Liver Dis 28: 188–200CrossRefPubMedGoogle Scholar
  31. 31.
    Chau T, Chan Y, Patch D, Tokanuga S, Greenslade L, Burroughs A (1998) Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding. Gut 43: 267–271PubMedCrossRefGoogle Scholar
  32. 32.
    Papatheodoridis G, Patch D, Webster G, Brooker J, Barnes E, Burroughs A (1999) Infection and hemostasis in decompensated cirrhosis: a prospective study using thrombelastography. Hepatology 29: 1085–1090CrossRefPubMedGoogle Scholar
  33. 33.
    Fernandez-Seara J, Prieto J, Quiroga J, et al (1989) Systemic and regional haemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure. Gastroenterology 97: 1304–1312PubMedGoogle Scholar
  34. 34.
    Moller S, Henriksen J (2008) Cardiovascular complications of cirrhosis. Gut 57: 268–278CrossRefPubMedGoogle Scholar
  35. 35.
    Russell J, Walley K, Singer J, et al (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358: 877–887CrossRefPubMedGoogle Scholar
  36. 36.
    Annane D, Sebille V, Charpentier C, et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288: 862–871CrossRefPubMedGoogle Scholar
  37. 37.
    Malbrain M, Chiumello D, Pelosi P, et al (2004) Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study. Intensive Care Med 30: 822–829CrossRefPubMedGoogle Scholar
  38. 38.
    Rajkovic IA, Williams R (1986) Abnormalities of neutrophil phagocytosis, intracellular killing and metabolic activity in alcoholic cirrhosis and hepatitis. Hepatology 6: 252–262CrossRefPubMedGoogle Scholar
  39. 39.
    Trevisani F, Castelli E, Foschi FG, et al (2002) Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome. Gut 50: 707–712CrossRefPubMedGoogle Scholar
  40. 40.
    Mookerjee R, Stadlbauer V, Lidder S, et al (2007) Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts outcome. Hepatology 46: 831–840CrossRefPubMedGoogle Scholar
  41. 41.
    Shawcross D, Wright G, Stadlbauer V, et al (2008) Ammonia impairs neutrophil phagocytic function in liver disease. Hepatology 48: 1202–1212CrossRefPubMedGoogle Scholar
  42. 42.
    Borroni G, Maggi A, Sangiovanni A, Cazzaniga M, Salerno F (2000) Clinical relevance of hyponatraemia for the hospital outcome of cirrhotic patients. Dig Liver Dis 32: 605–610CrossRefPubMedGoogle Scholar
  43. 43.
    Olde Damink S, Jalan R, Deutz N, et al (2003) The kidney plays a major role in the hyperammonemia seen after a simulated or actual upper gastrointestinal bleeding in patients with cirrhosis. Hepatology 37: 1277–1285CrossRefPubMedGoogle Scholar
  44. 44.
    Walker S, Stiehl A, Raedsch R, Kommerell B (1986) Terlipressin in bleeding oesphageal varices: a placebo-controlled, double blind study. Hepatology 6: 112–115CrossRefPubMedGoogle Scholar
  45. 45.
    Monescillo A, Martinez-Lagares F, Ruiz-del-Arbol L, et al (2004) Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology 40: 793–801PubMedGoogle Scholar
  46. 46.
    Laine L, Planas R, Nevens F, Banares R, Patch D, Bosch J (2006) Treatment of the acute bleeding episode. In: De Franchis R (ed) Portal Hypertension IV: Proceedings of the Fourth Baveno International Consensus Workshop. Blackwell Publishing, Boston, pp217–242Google Scholar
  47. 47.
    Salerno F, Gerbes A, Gines P, Wong F, Arroyo V (2007) Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut 56: 1310–1318PubMedGoogle Scholar
  48. 48.
    Ortega R, Gines P, Uriz J, et al (2002) Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, non randomised study. Hepatology 36: 941–948PubMedGoogle Scholar
  49. 49.
    VA/NIH Acute Renal Failure Trial Network (2008) Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 359: 7–20CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • D. Shawcross
    • 1
  • J. Wendon
    • 2
  1. 1.Department of HepatologyKing’s College HospitalLondonUK
  2. 2.Liver Intensive Care Unit and Institute of Liver StudiesKing’s College HospitalLondonUK

Personalised recommendations