Acute liver failure (ALF) is defined as the sudden onset of coagulopathy (i.e. elevated INR) and mental status changes in a patient without preexisting liver disease. ALF is an uncommon disorder that can arise from a multitude of etiologies with acetaminophen (APAP) overdose accounting for nearly 50% of adult cases in the US. The clinical course of ALF is highly variable but associated with a high rate of morbidity and mortality. All ALF patients with cerebral edema, renal failure, or an etiology that is associated with a low likelihood of spontaneous recovery should be urgently referred for emergency liver transplant evaluation. Aggressive hemodynamic support, mechanical intubation, preemptive treatment of bacterial and fungal infections, and use of disease specific therapy in selected patients is recommended. Cerebral edema, which is notoriously difficult to diagnose, may arise in 50–70% of ALF patients due to hyperammonemia, high levels of circulating proinflammatory cytokines, and cerebral hyperperfusion. Administration of blood products along with recombinant factor VIIa can allow for the placement of an intracranial pressure (ICP) monitor in ALF patients with stage III or IV encephalopathy. ICP monitors allow intensivists to rationally administer osmotic agents (mannitol and hypertonic saline), vasopressors, and pentobarbital to maintain an adequate cerebral perfusion pressure. Outcomes in ALF patients are largely determined by the etiology of ALF, maximal degree of encephalopathy, and development of multi-organ failure. ICU interventions can help support native liver recovery and also help bridge patients with progressive ALF to emergency liver transplantation.
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The authors would like to thank Dr. William M. Lee of the University of Texas Southwestern, Dallas, for data used in Fig. 70.3. The authors would also like to thank Dr. Krishna Rajajee of the Neuro Critical Care Division at the University of Michigan for his careful review of the manuscript.
Grant Support: Support for Dr. Fontana provided in part by the National Institutes of Diabetes, Digestive, and Kidney Diseases (DK U-01-58369) as a member of the Acute Liver Failure Study Group. Support for Dr. Mellinger provided by the AASLD Advanced Transplant Hepatology Fellowship.
Lee WM. Recent developments in acute liver failure. Best Pract Res Clin Gastroenterol. 2012;26(1):3–16.CrossRefGoogle Scholar
Bari K, Fontana RJ. Acetaminophen overdose: what practitioners need to know. Clin Liver Dis. 2014;4(1):17–21.CrossRefGoogle Scholar
Craig DGN, Bates CM, Davidson JS, Martin KG, Hayes PC, Simpson KJ. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity. Br J Clin Pharmacol. 2012 Feb;73(2):285–94.CrossRefGoogle Scholar
Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55(3):965–7.CrossRefGoogle Scholar
Bernal W, Donaldson N, Wyncoll D, Wendon J. Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet. 2002;359(9306):558–63.CrossRefGoogle Scholar
Koch DG, Tillman H, Durkalski V, Lee WM, Reuben A. Development of a model to predict transplant-free survival of patients with acute liver failure. Clin Gastroenterol Hepatol. 2016;14(8):1199–206.CrossRefGoogle Scholar
Stravitz RT, Lisman T, Luketic VA, Sterling RK, Puri P, Fuchs M, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol. 2012;56(1):129–36.CrossRefGoogle Scholar
Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM. Bleeding complications in acute liver failure. Hepatology. 2018;67:1931–42.CrossRefGoogle Scholar
Shawcross DL, Davies NA, Mookerjee RP, Hayes PC, Williams R, Lee A, et al. Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. Hepatology. 2004;39(2):471–5.CrossRefGoogle Scholar
Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology. 2002;36(2):395–402.CrossRefGoogle Scholar
Rakela J, Mosley JW, Edwards VM, Govindarajan S, Alpert E. A double-blinded, randomized trial of hydrocortisone in acute hepatic failure. The acute hepatic failure study group. Dig Dis Sci. 1991;36(9):1223–8.CrossRefGoogle Scholar
Tujios SR, Hynan LS, Vazquez MA, Larson AM, Seremba E, Sanders CM, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol. 2015;13(2):352–9.CrossRefGoogle Scholar
Davenport A, Will EJ, Davidson AM. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med. 1993;21(3):328–38.CrossRefGoogle Scholar
Cardoso FS, Gottfried M, Tujios S, Olson JC, Kaverllas CJ. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology. 2018;67:711–20.CrossRefGoogle Scholar
Rolando N, Gimson A, Wade J, Philpott-Howard J, Casewell M, Williams R. Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure. Hepatology. 1993;17(2):196–201.CrossRefGoogle Scholar
Karvellas CJ, Fix OK, Battenhouse H, Durkalski V, Sanders C, Lee WM, et al. Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study. Crit Care Med. 2014;42(5):1157–67.CrossRefGoogle Scholar
Rajajee V, Fontana RJ, Courey AJ, Patil PG. Protocol based invasive intracranial pressure monitoring in acute liver failure: feasability, safety and impact on management. Crit Care. 2017;21:178–84.CrossRefGoogle Scholar
Kheirbek T, Pascual JL. Hypertonic saline for the treatment of intracranial hypertension. Curr Neurol Neurosci Rep. 2014;14(9):482.CrossRefGoogle Scholar
Shami VM, Caldwell SH, Hespenheide EE, Arseneau KO, Bickston SJ, Macik BG. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl. 2003;9(2):138–43.CrossRefGoogle Scholar
Pavese P, Bonadona A, Beaubien J, Labrecque P, Pernod G, Letoublon C, et al. FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: a report of four cases. Can J Anaesth. 2005;52(1):26–9.CrossRefGoogle Scholar
Le TV, Rumbak MJ, Liu SS, Alsina AE, van Loveren H, Agazzi S. Insertion of intracranial pressure monitors in fulminant hepatic failure patients: early experience using recombinant factor VII. Neurosurgery. 2010;66(3):455–8; discussion 458CrossRefGoogle Scholar
Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999;29(3):648–53.CrossRefGoogle Scholar
Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006;55(1):98–104.CrossRefGoogle Scholar
Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46(6):1844–52.CrossRefGoogle Scholar
Karvellas CJ, Todd Stravitz R, Battenhouse H, Lee WM, Schilsky ML, US Acute Liver Failure Study Group. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl. 2015;21(1):4–12.CrossRefGoogle Scholar
Jalan R, Olde Damink SWM, Deutz NEP, Hayes PC, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology. 2004;127(5):1338–46.CrossRefGoogle Scholar
Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, 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.CrossRefGoogle Scholar
Willars C. Update in intensive care medicine: acute liver failure. Initial management, supportive treatment and who to transplant. Curr Opin Crit Care. 2014;20(2):202–9.CrossRefGoogle Scholar
O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439–45.CrossRefGoogle Scholar