Acute Liver Failure

  • Amar Gupta
  • Chad G. Ball


Acute liver failure (ALF) is characterized by typical biochemical alterations, coagulopathy, encephalopathy, and multi-organ dysfunction. While viral hepatitis is the most common source of ALF worldwide, the majority of cases of ALF in the Western world are secondary to acetaminophen toxicity. Less common causes of ALF include ischemia, Wilson’s disease, Budd-Chiari syndrome, autoimmune hepatitis, and toxic mushroom ingestion. Furthermore, a significant number of ALF cases have no identifiable cause. Management of ALF focuses on supportive measures in an intensive care unit, with few liver-directed therapies available. Currently, liver transplantation remains the only treatment for ALF in patients who do not regain adequate liver function.


Liver failure Hepatitis Encephalopathy Multiple organ dysfunction syndrome Liver transplantation 


  1. 1.
    Bernal W, et al. Acute liver failure. Lancet. 2010;376(9736):190–201.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bernuau J, Rueff B, Benhamou JP. Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis. 1986;6(2):97–106.CrossRefPubMedGoogle Scholar
  3. 3.
    Mochida S, et al. Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. Hepatol Res. 2008;38(10):970–9.CrossRefPubMedGoogle Scholar
  4. 4.
    O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. 1993;342(8866):273–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369(26):2525–34.CrossRefPubMedGoogle Scholar
  6. 6.
    Dalton HR, et al. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008;8(11):698–709.CrossRefPubMedGoogle Scholar
  7. 7.
    Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA. 2005;294(2):194–201.CrossRefPubMedGoogle Scholar
  8. 8.
    Taylor RM, et al. Fulminant hepatitis A virus infection in the United States: incidence, prognosis, and outcomes. Hepatology. 2006;44(6):1589–97.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Patra S, et al. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med. 2007;147(1):28–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Katz LH, et al. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat. 2008;15(2):89–102.PubMedGoogle Scholar
  11. 11.
    Mindikoglu AL, Regev A, Schiff ER. Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention. Clin Gastroenterol Hepatol. 2006;4(9):1076–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol. 2012;9(3):156–66.CrossRefPubMedGoogle Scholar
  13. 13.
    Ichai P, Samuel D. Etiology and prognosis of fulminant hepatitis in adults. Liver Transpl. 2008;14(Suppl 2):S67–79.CrossRefPubMedGoogle Scholar
  14. 14.
    Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016;16(Suppl 6):s104–9.CrossRefGoogle Scholar
  15. 15.
    Reuben A, et al. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065–76.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bernal W, et al. Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience. J Hepatol. 2009;50(2):306–13.CrossRefPubMedGoogle Scholar
  17. 17.
    Schindl MJ, et al. The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection. Gut. 2005;54(2):289–96.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    van den Broek MA, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int. 2008;28(6):767–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Schnitzbauer AA, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255(3):405–14.CrossRefPubMedGoogle Scholar
  20. 20.
    de Graaf W, et al. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg. 2011;98(6):825–34.CrossRefPubMedGoogle Scholar
  21. 21.
    Balzan S, et al. The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242(6):824–8, discussion 828–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rahbari NN, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149(5):713–24.CrossRefPubMedGoogle Scholar
  23. 23.
    Rahbari NN, et al. The predictive value of postoperative clinical risk scores for outcome after hepatic resection: a validation analysis in 807 patients. Ann Surg Oncol. 2011;18(13):3640–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Waseem N, Chen PH. Hypoxic hepatitis: a review and clinical update. J Clin Transl Hepatol. 2016;4(3):263–8.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Niranjan-Azadi AM, et al. Ammonia level and mortality in acute liver failure: a single-center experience. Ann Transplant. 2016;21:479–83.CrossRefPubMedGoogle Scholar
  26. 26.
    Kodali S, McGuire BM. Diagnosis and management of hepatic encephalopathy in fulminant hepatic failure. Clin Liver Dis. 2015;19(3):565–76.CrossRefPubMedGoogle Scholar
  27. 27.
    Wang DW, Yin YM, Yao YM. Advances in the management of acute liver failure. World J Gastroenterol. 2013;19(41):7069–77.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Murphy N, et al. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology. 2004;39(2):464–70.CrossRefPubMedGoogle Scholar
  29. 29.
    Vaquero J, Rose C, Butterworth RF. Keeping cool in acute liver failure: rationale for the use of mild hypothermia. J Hepatol. 2005;43(6):1067–77.CrossRefPubMedGoogle Scholar
  30. 30.
    Bernal W, et al. A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure. J Hepatol. 2016;65(2):273–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Audimoolam VK, et al. Predicting fluid responsiveness in acute liver failure: a prospective study. Anesth Analg. 2017;124(2):480–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Maheshwari R, Subramanian RM. On the brink of death: managing acute liver failure. Am J Gastroenterol. 2016;112(2):200–6.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Barton CA. Treatment of coagulopathy related to hepatic insufficiency. Crit Care Med. 2016;44(10):1927–33.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol. 2002;37(2):280–7.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Leithead JA, et al. The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut. 2009;58(3):443–9.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Davenport A. Continuous renal replacement therapies in patients with liver disease. Semin Dial. 2009;22(2):169–72.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Slack AJ, et al. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int. 2014;34(1):42–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Moore K. Renal failure in acute liver failure. Eur J Gastroenterol Hepatol. 1999;11(9):967–75.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    O'Riordan A, et al. Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity. Nephrol Dial Transplant. 2011;26(11):3501–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ramos Figueira ER, et al. Nutritional support for fulminant hepatitis. Nutr Hosp. 2015;32(6):2427–32.PubMedGoogle Scholar
  41. 41.
    Montejo González JC, et al. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: update. Consensus SEMICYUC-SENPE: liver failure and liver transplantation. Nutr Hosp. 2011;26(Suppl 2):27–31.PubMedGoogle Scholar
  42. 42.
    Rabinowich L, et al. Clinical management of acute liver failure: results of an international multi-center survey. World J Gastroenterol. 2016;22(33):7595–603.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Vaquero J, et al. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology. 2003;125(3):755–64.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Karvellas CJ, et al. Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study. Clin Gastroenterol Hepatol. 2014;12(11):1942–9.e1.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Keays R, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ. 1991;303(6809):1026–9.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lee WM, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856–64, 864.e1CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kumar M, et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007;45(1):97–101.CrossRefPubMedGoogle Scholar
  48. 48.
    Miyake Y, et al. Lamivudine treatment improves the prognosis of fulminant hepatitis B. Intern Med. 2008;47(14):1293–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Tillmann HL, et al. Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat. 2006;13(4):256–63.CrossRefPubMedGoogle Scholar
  50. 50.
    Ichai P, et al. Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis. Liver Transpl. 2007;13(7):996–1003.CrossRefPubMedGoogle Scholar
  51. 51.
    O'Grady JG, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439–45.CrossRefPubMedGoogle Scholar
  52. 52.
    Flamm SL, et al. American Gastroenterological Association Institute guidelines for the diagnosis and management of acute liver failure. Gastroenterology. 2017;152(3):644–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Goldaracena N, et al. Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure. Am J Transplant. 2015;15(6):1591–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Kaido T, et al. Liver transplantation in adults with acute liver failure: a single center experience over a period of 15 years. Hepato-Gastroenterology. 2015;62(140):937–41.PubMedGoogle Scholar
  55. 55.
    Kirnap M, et al. Liver transplant for fulminant hepatic failure: a single-center experience. Exp Clin Transplant. 2015;13(4):339–43.PubMedGoogle Scholar
  56. 56.
    Park SJ, et al. Emergency adult-to-adult living-donor liver transplantation for acute liver failure in a hepatitis B virus endemic area. Hepatology. 2010;51(3):903–11.PubMedGoogle Scholar
  57. 57.
    Gonzalez HC, Jafri SM, Gordon SC. Management of acute hepatotoxicity including medical agents and liver support systems. Clin Liver Dis. 2017;21(1):163–80.CrossRefPubMedGoogle Scholar
  58. 58.
    Saliba F, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med. 2013;159(8):522–31.CrossRefPubMedGoogle Scholar
  59. 59.
    Rifai K, et al. Prometheus--a new extracorporeal system for the treatment of liver failure. J Hepatol. 2003;39(6):984–90.CrossRefPubMedGoogle Scholar
  60. 60.
    Larsen FS, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol. 2016;64(1):69–78.CrossRefPubMedGoogle Scholar
  61. 61.
    Demetriou AA, et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg. 2004;239(5):660–7; discussion 667–70.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Amar Gupta
    • 1
  • Chad G. Ball
    • 2
  1. 1.Department of General SurgeryFoothills Medical CenterCalgaryCanada
  2. 2.Department of SurgeryUniversity of Calgary, Foothills Medical CenterCalgaryCanada

Personalised recommendations