Acute Liver Failure

Abstract

Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. This article focuses on the diagnosis and management of ALF. We provide a detailed review of the common etiologies of ALF, including acetaminophen overdose, viral hepatitis, drug-induced liver injury, Wilson's disease, and autoimmune hepatitis. The article then addresses how to recognize ALF and reviews the role of common laboratory and imaging tests in establishing this diagnosis. The remainder of the article details the management of hepatic and extrahepatic organ dysfunctions in ALF. The article concludes with a discussion regarding the prognostication of patients with ALF and the criteria for considering liver transplantation.

Keywords

acute liver failure - hepatic encephalopathy - acute renal failure - intracranial hypertension - acetaminophen toxicity

• References

• 1 Blackmore L, Bernal W. Acute liver failure. Clin Med (Lond) 2015; 15 (05) 468-472
• 2 Cardoso FS, Marcelino P, Bagulho L, Karvellas CJ. Acute liver failure: an up-to-date approach. J Crit Care 2017; 39: 25-30
• 3 Kandiah PA, Olson JC, Subramanian RM. Emerging strategies for the treatment of patients with acute hepatic failure. Curr Opin Crit Care 2016; 22 (02) 142-151
• 4 Bernal W, Auzinger G, Sizer E, Wendon J. Intensive care management of acute liver failure. Semin Liver Dis 2008; 28 (02) 188-200
• 5 Bernsmeier C, Antoniades CG, Wendon J. What's new in acute liver failure?. Intensive Care Med 2014; 40 (10) 1545-1548
• 6 Baudouin SV, Howdle P, O'Grady JG, Webster NR. Acute lung injury in fulminant hepatic failure following paracetamol poisoning. Thorax 1995; 50 (04) 399-402
• 7 Koch DG, Speiser JL, Durkalski V. , et al. The natural history of severe acute liver injury. Am J Gastroenterol 2017; 112 (09) 1389-1396
• 8 Lee WM, Squires Jr RH, Nyberg SL, Doo E, Hoofnagle JH. Acute liver failure: summary of a workshop. Hepatology 2008; 47 (04) 1401-1415
• 9 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 (03) 965-967
• 10 Gulmez SE, Larrey D, Pageaux GP. , et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study. Drug Saf 2013; 36 (02) 135-144
• 11 Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2006; (02) CD003328
• 12 Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. BMJ 1979; 2 (6198): 1097-1100
• 13 Yang R, Miki K, He X, Killeen ME, Fink MP. Prolonged treatment with N-acetylcysteine delays liver recovery from acetaminophen hepatotoxicity. Crit Care 2009; 13 (02) R55
• 14 Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med 2003; 31 (01) 299-305
• 15 Lee WM, Hynan LS, Rossaro L. , et al; Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009; 137 (03) 856-864 , 864.e1
• 16 Shalimar, Acharya SK. Management in acute liver failure. J Clin Exp Hepatol 2015; 5 (Suppl. 01) S104-S115
• 17 Singh S, Hynan LS, Lee WM. ; Acute Liver Failure Study Group. Improvements in hepatic serological biomarkers are associated with clinical benefit of intravenous N-acetylcysteine in early stage non-acetaminophen acute liver failure. Dig Dis Sci 2013; 58 (05) 1397-1402
• 18 Habib S, Shaikh OS. Drug-induced acute liver failure. Clin Liver Dis 2017; 21 (01) 151-162
• 19 Ichai P, Laurent-Bellue A, Saliba F. , et al. Acute liver failure/injury related to drug reaction with eosinophilia and systemic symptoms: outcomes and prognostic factors. Transplantation 2017; 101 (08) 1830-1837
• 20 Thiim M, Friedman LS. Hepatotoxicity of antibiotics and antifungals. Clin Liver Dis 2003; 7 (02) 381-399 , vi–vii
• 21 Russo MW, Scobey M, Bonkovsky HL. Drug-induced liver injury associated with statins. Semin Liver Dis 2009; 29 (04) 412-422
• 22 Mumtaz K, Azam Z, Hamid S. , et al. Role of N-acetylcysteine in adults with non-acetaminophen-induced acute liver failure in a center without the facility of liver transplantation. Hepatol Int 2009; 3 (04) 563-570
• 23 Czaja AJ. Drug-induced autoimmune-like hepatitis. Dig Dis Sci 2011; 56 (04) 958-976
• 24 Dignan FL, Wynn RF, Hadzic N. , et al; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol 2013; 163 (04) 444-457
• 25 Bismuth H, Samuel D, Castaing D. , et al. Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The Paul Brousse experience. Ann Surg 1995; 222 (02) 109-119
• 26 Jayakumar S, Chowdhury R, Ye C, Karvellas CJ. Fulminant viral hepatitis. Crit Care Clin 2013; 29 (03) 677-697
• 27 Noor A, Panwala A, Forouhar F, Wu GY. Hepatitis caused by herpes viruses: a review. J Dig Dis 2018
• 28 O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97 (02) 439-445
• 29 Younis BB, Arshad R, Khurhsid S, Masood J, Nazir F, Tahira M. Fulminant hepatic failure (FHF) due to acute hepatitis C. Pak J Med Sci 2015; 31 (04) 1009-1011
• 30 Lightsey JM, Rockey DC. Current concepts in ischemic hepatitis. Curr Opin Gastroenterol 2017; 33 (03) 158-163
• 31 Ma M, Falloon K, Chen PH. , et al. The role of liver transplantation in alcoholic hepatitis. J Intensive Care Med 2018 Doi: 10.1177/0885066618780339
• 32 Bernuau J, Goudeau A, Poynard T. , et al. Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology 1986; 6 (04) 648-651
• 33 Wang CY, Zhao P, Liu WW. ; Acute Liver Failure Study Team. Acute liver failure caused by severe acute hepatitis B: a case series from a multi-center investigation. Ann Clin Microbiol Antimicrob 2014; 13: 23
• 34 Frias M, López-López P, Rivero A, Rivero-Juarez A. Role of hepatitis E virus infection in acute-on-chronic liver failure. BioMed Res Int 2018; 2018: 9098535
• 35 Seijo S, Plessier A, Hoekstra J. , et al; European Network for Vascular Disorders of the Liver. Good long-term outcome of Budd-Chiari syndrome with a step-wise management. Hepatology 2013; 57 (05) 1962-1968
• 36 Zhang F, Wang C, Li Y. The outcomes of interventional treatment for Budd-Chiari syndrome: systematic review and meta-analysis. Abdom Imaging 2015; 40 (03) 601-608
• 37 Rizvi S, Gawrieh S. Autoimmune hepatitis in the elderly: diagnosis and pharmacologic management. Drugs Aging 2018; 35 (07) 589-602
• 38 Singanayagam A, Bernal W. Update on acute liver failure. Curr Opin Crit Care 2015; 21 (02) 134-141
• 39 Yasui S, Fujiwara K, Yonemitsu Y, Oda S, Nakano M, Yokosuka O. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol 2011; 46 (03) 378-390
• 40 Pfeiffenberger J, Weiss KH, Stremmel W. Wilson disease: symptomatic liver therapy. Handb Clin Neurol 2017; 142: 205-209
• 41 Huang Y, Takatsuki M, Soyama A. , et al. Living donor liver transplantation for Wilson's disease associated with fulminant hepatic failure: a case report. Am J Case Rep 2018; 19: 304-308
• 42 Khan R, Koppe S. Modern management of acute liver failure. Gastroenterol Clin North Am 2018; 47 (02) 313-326
• 43 Collado Ferrer M, Collado Ferrer L, Serrano A. Acute fatty liver of pregnancy. Bol Asoc Med P R 2010; 102 (04) 51-53
• 44 Ronen J, Shaheen S, Steinberg D, Justus KR. Acute fatty liver of pregnancy: a thorough examination of a harmful obstetrical syndrome and its counterparts. Cureus 2018; 10 (02) e2164
• 45 Rabinowich L, Wendon J, Bernal W, Shibolet O. Clinical management of acute liver failure: results of an international multi-center survey. World J Gastroenterol 2016; 22 (33) 7595-7603
• 46 Bernal W, Hyyrylainen A, Gera A. , et al. Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol 2013; 59 (01) 74-80
• 47 Nakao M, Nakayama N, Uchida Y. , et al. Nationwide survey for acute liver failure and late-onset hepatic failure in Japan. J Gastroenterol 2018; 53 (06) 752-769
• 48 Bernal W, Williams R. Beyond KCH selection and options in acute liver failure. Hepatol Int 2018; 12 (03) 204-213
• 49 Fikatas P, Lee JE, Sauer IM. , et al. APACHE III score is superior to King's College Hospital criteria, MELD score and APACHE II score to predict outcomes after liver transplantation for acute liver failure. Transplant Proc 2013; 45 (06) 2295-2301
• 50 Cordoba J. Hepatic encephalopathy: from the pathogenesis to the new treatments. ISRN Hematol 2014; 2014: 236268
• 51 Ciećko-Michalska I, Szczepanek M, Słowik A, Mach T. Pathogenesis of hepatic encephalopathy. Gastroenterol Res Pract 2012; 2012: 642108
• 52 Salgado M, Cortes Y. Hepatic encephalopathy: etiology, pathogenesis, and clinical signs. Compend Contin Educ Vet 2013; 35 (06) E1-E8 , quiz E9
• 53 Toris GT, Bikis CN, Tsourouflis GS, Theocharis SE. Hepatic encephalopathy: an updated approach from pathogenesis to treatment. Med Sci Monit 2011; 17 (02) RA53-RA63
• 54 Basile AS, Jones EA. Ammonia and GABA-ergic neurotransmission: interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology 1997; 25 (06) 1303-1305
• 55 Bosoi CR, Rose CF. Elevated cerebral lactate: implications in the pathogenesis of hepatic encephalopathy. Metab Brain Dis 2014; 29 (04) 919-925
• 56 Maddison JE. Hepatic encephalopathy. Current concepts of the pathogenesis. J Vet Intern Med 1992; 6 (06) 341-353
• 57 Desjardins P, Du T, Jiang W, Peng L, Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure: role of glutamine redefined. Neurochem Int 2012; 60 (07) 690-696
• 58 Häussinger D. [Hepatic encephalopathy: clinical aspects and pathogenesis]. Dtsch Med Wochenschr 2004; 129 (Suppl. 02) S66-S67
• 59 Shawcross DL, Shabbir SS, Taylor NJ, Hughes RD. Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 2010; 51 (03) 1062-1069
• 60 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 (06) 1844-1852
• 61 Quero Guillén JC, Carmona Soria I, García Montes JM, Jiménez Sáenz M, Herrerías Gutiérrez JM. Hepatic encephalopathy: nomenclature, pathogenesis and treatment. Rev Esp Enferm Dig 2003; 95 (02) 135-142 , 127–134
• 62 Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013; 369 (26) 2525-2534
• 63 Larson AM. Diagnosis and management of acute liver failure. Curr Opin Gastroenterol 2010; 26 (03) 214-221
• 64 Davenport A. Management of acute kidney injury in liver disease. Contrib Nephrol 2010; 165: 197-205
• 65 Davenport A. Continuous renal replacement therapies in patients with liver disease. Semin Dial 2009; 22 (02) 169-172
• 66 Davenport A. Continuous renal replacement therapy for liver disease. Hemodial Int 2003; 7 (04) 348-352
• 67 Davenport A, Sheikh MF, Lamb E, Agarwal B, Jalan R. Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit?. Kidney Int 2017; 92 (05) 1058-1070
• 68 O'Brien Z, Cass A, Cole L. , et al; RENAL Study Investigators and the Australian and New Zealand Intensive Care Clinical Trials Group. Higher versus lower continuous renal replacement therapy intensity in critically ill patients with liver dysfunction. Blood Purif 2018; 45 (1-3): 36-43
• 69 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 (03) 328-338
• 70 Gupta S, Fenves AZ, Hootkins R. The role of RRT in hyperammonemic patients. Clin J Am Soc Nephrol 2016; 11 (10) 1872-1878
• 71 Ede RJ, Gimson AE, Bihari D, Williams R. Controlled hyperventilation in the prevention of cerebral oedema in fulminant hepatic failure. J Hepatol 1986; 2 (01) 43-51
• 72 Blei AT, Olafsson S, Webster S, Levy R. Complications of intracranial pressure monitoring in fulminant hepatic failure. Lancet 1993; 341 (8838): 157-158
• 73 Karvellas CJ, Fix OK, Battenhouse H, Durkalski V, Sanders C, Lee WM. ; U S Acute Liver Failure Study Group. Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study. Crit Care Med 2014; 42 (05) 1157-1167
• 74 Vaquero J, Fontana RJ, Larson AM. , et al. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transpl 2005; 11 (12) 1581-1589
• 75 Stravitz RT, Kramer AH, Davern T. , et al; Acute Liver Failure Study Group. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med 2007; 35 (11) 2498-2508
• 76 Rajajee V, Fontana RJ, Courey AJ, Patil PG. Protocol based invasive intracranial pressure monitoring in acute liver failure: feasibility, safety and impact on management. Crit Care 2017; 21 (01) 178
• 77 Krisl JC, Meadows HE, Greenberg CS, Mazur JE. Clinical usefulness of recombinant activated factor VII in patients with liver failure undergoing invasive procedures. Ann Pharmacother 2011; 45 (11) 1433-1438
• 78 Rajajee V, Williamson CA, Fontana RJ, Courey AJ, Patil PG. Noninvasive intracranial pressure assessment in acute liver failure. Neurocrit Care 2018
• 79 Polson J, Lee WM. ; American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatology 2005; 41 (05) 1179-1197
• 80 Diringer MN, Zazulia AR. Osmotic therapy: fact and fiction. Neurocrit Care 2004; 1 (02) 219-233
• 81 Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology 2004; 39 (02) 464-470
• 82 Canalese J, Gimson AE, Davis C, Mellon PJ, Davis M, Williams R. Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure. Gut 1982; 23 (07) 625-629
• 83 Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology 2004; 127 (05) 1338-1346
• 84 Larson AC, Jamrogowicz JL, Kulikowicz E. , et al. Cerebrovascular autoregulation after rewarming from hypothermia in a neonatal swine model of asphyxic brain injury. J Appl Physiol (1985) 2013; 115 (10) 1433-1442
• 85 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 (01) 4-12
• 86 Saigal S, Sharma JP, Dhurwe R, Kumar S, Gurjar M. Targeted temperature management: current evidence and practices in critical care. Indian J Crit Care Med 2015; 19 (09) 537-546
• 87 Vaquero J. Therapeutic hypothermia in the management of acute liver failure. Neurochem Int 2012; 60 (07) 723-735
• 88 Tofteng F, Larsen FS. The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure. J Cereb Blood Flow Metab 2004; 24 (07) 798-804
• 89 Wigmore SJ, Walsh TS, Lee A, Ross JA. Pro-inflammatory cytokine release and mediation of the acute phase protein response in fulminant hepatic failure. Intensive Care Med 1998; 24 (03) 224-229
• 90 Tranah TH, Vijay GK, Ryan JM, Shawcross DL. Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis 2013; 28 (01) 1-5
• 91 Zider AD, Zopey R, Garg R, Wang X, Wang TS, Deng JC. Prognostic significance of infections in critically ill adult patients with acute liver injury: a retrospective cohort study. Liver Int 2016; 36 (08) 1143-1150
• 92 Rolando N, Philpott-Howard J, Williams R. Bacterial and fungal infection in acute liver failure. Semin Liver Dis 1996; 16 (04) 389-402
• 93 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 (4 Pt 1): 734-739
• 94 Wade J, Rolando N, Philpott-Howard J, Wendon J. Timing and aetiology of bacterial infections in a liver intensive care unit. J Hosp Infect 2003; 53 (02) 144-146
• 95 Vaquero J, Polson J, Chung C. , et al. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 2003; 125 (03) 755-764
• 96 Rolando N, Harvey F, Brahm J. , et al. Fungal infection: a common, unrecognised complication of acute liver failure. J Hepatol 1991; 12 (01) 1-9
• 97 Audimoolam VK, McPhail MJ, Willars C. , et al. Predicting fluid responsiveness in acute liver failure: a prospective study. Anesth Analg 2017; 124 (02) 480-486
• 98 Olson JC. Intensive care management of patients with cirrhosis. Curr Treat Options Gastroenterol 2018; 16 (02) 241-252
• 99 Olson JC, Wendon JA, Kramer DJ. , et al. Intensive care of the patient with cirrhosis. Hepatology 2011; 54 (05) 1864-1872
• 100 Chung C, Vaquero J, Gottstein J, Blei AT. Vasopressin accelerates experimental ammonia-induced brain edema in rats after portacaval anastomosis. J Hepatol 2003; 39 (02) 193-199
• 101 Eefsen M, Dethloff T, Frederiksen HJ, Hauerberg J, Hansen BA, Larsen FS. Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support. J Hepatol 2007; 47 (03) 381-386
• 102 Harry R, Auzinger G, Wendon J. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Hepatology 2002; 36 (02) 395-402
• 103 Audimoolam VK, McPhail MJ, Wendon JA. , et al. Lung injury and its prognostic significance in acute liver failure. Crit Care Med 2014; 42 (03) 592-600
• 104 Blonski W, Siropaides T, Reddy KR. Coagulopathy in liver disease. Curr Treat Options Gastroenterol 2007; 10 (06) 464-473
• 105 Kerr R, Newsome P, Germain L. , et al. Effects of acute liver injury on blood coagulation. J Thromb Haemost 2003; 1 (04) 754-759
• 106 Stravitz RT, Bowling R, Bradford RL. , et al. Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure. Hepatology 2013; 58 (01) 304-313
• 107 Scărlătescu E, Tomescu DR. Prothrombotic state in a patient with acute liver failure: the question of anticoagulation. Semin Cardiothorac Vasc Anesth 2018; 22 (02) 174-179
• 108 Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg 2009; 108 (03) 759-769
• 109 Munoz SJ, Rajender Reddy K, Lee W. ; Acute Liver Failure Study Group. The coagulopathy of acute liver failure and implications for intracranial pressure monitoring. Neurocrit Care 2008; 9 (01) 103-107
• 110 Brown JB, Emerick KM, Brown DL, Whitington PF, Alonso EM. Recombinant factor VIIa improves coagulopathy caused by liver failure. J Pediatr Gastroenterol Nutr 2003; 37 (03) 268-272
• 111 Pham HP, Hsu SX, Parker-Jones S, Samstein B, Diuguid D, Schwartz J. Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience. Vox Sang 2014; 106 (01) 75-82
• 112 Vogel GE. Early treatment with AT III in acute liver failure. Behring Inst Mitt 1983; (73) 79-93 . PMID: 6679286
• 113 DellaVolpe J, Al-Khafaji A. Acute kidney injury before and after liver transplant. J Intensive Care Med 2018 Doi: 10.1177/0885066618790558
• 114 Jovanović I, Tešić M, Antonijević N. , et al. Acute renal failure and hepatocellular damage as presenting symptoms of type II aortic dissection. Srp Arh Celok Lek 2016; 144 (5-6): 320-324
• 115 Arora V, Maiwall R, Vijayaraghavan R. , et al. Terlipressin is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology 2018 Doi: 10.1002/hep.30208
• 116 Fujiwara K, Yasui S, Yokosuka O, Oda S, Kato N. A role of renal replacement therapy for acute liver failure. Hepatology 2018 Doi: 10.1002/hep.30081
• 117 Leventhal TM, Liu KD. What a nephrologist needs to know about acute liver failure. Adv Chronic Kidney Dis 2015; 22 (05) 376-381
• 118 McPhail MJ, Farne H, Senvar N, Wendon JA, Bernal W. Ability of King's College criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis. Clin Gastroenterol Hepatol 2016; 14 (04) 516-525.e5 , quiz e43–e45
• 119 McPhail MJ, Wendon JA, Bernal W. Meta-analysis of performance of Kings's College Hospital criteria in prediction of outcome in non-paracetamol-induced acute liver failure. J Hepatol 2010; 53 (03) 492-499