Acute liver failure

Last updated: June 5, 2023

Summarytoggle arrow icon

Acute liver failure (ALF) is a severe condition seen in individuals without previous hepatic disease, and it is characterized by rapidly progressive liver injury, hepatic encephalopathy, and impaired synthetic function, which results in coagulopathy. If these features occur in individuals with prior hepatic disease, it is considered acute-on-chronic liver failure. The most common causes are infections (e.g., viral hepatitis) and drug toxicity (e.g., acetaminophen ingestion). Hepatic encephalopathy may be accompanied by jaundice and nonspecific symptoms such as nausea, vomiting, and fatigue. The diagnosis is confirmed by identifying an elevation of hepatic enzymes and an altered coagulation panel in patients with encephalopathy. Clinicians should maintain a high index of suspicion and aim to confirm the diagnosis as quickly as possible in order to start management early. Patients with ALF are usually critically ill and require admission to a critical care unit for extensive supportive treatment. The prognosis is poor, and most patients require urgent liver transplantation as definitive treatment.

Definitiontoggle arrow icon

  • Acute liver failure (ALF): a condition characterized by a rapidly progressive (within a period of 26 weeks) and severe acute liver injury, defined as impairment of synthetic function (i.e., coagulopathy) and encephalopathy, in an individual without previous hepatic disease
    • Subtypes are defined according to the amount of time it takes for encephalopathy to develop. [1][2][3]
      • Hyperacute liver failure: 0–1 weeks
      • Acute (fulminant) liver failure: 1–3 weeks
      • Subacute liver failure: Encephalopathy develops slowly, after ∼ 3 weeks and up to ∼ 26 weeks from the onset of other symptoms.
  • Chronic liver disease (CLD): a condition characterized by progressive deterioration of hepatic function over at least 26–28 weeks (∼ 6 months), e.g., cirrhosis. [2]
  • Acute decompensation of CLD: An episode of acute worsening of chronic liver disease manifestations (e.g., ascites, hepatic encephalopathy, GI bleeding, jaundice, infection), which can be due to a precipitant or progression of the underlying illness. [4]
  • Acute-on-chronic liver failure (ACLF): A distinct syndrome involving acute decompensation of CLD accompanied by multiorgan failure and significant short-term mortality. [4][5][6]

Etiologytoggle arrow icon

Etiology of acute liver failure [1][3][7][8]
Hepatotoxic medications
Other exogenous toxins

Acute liver failure is idiopathic in 20–45% of cases, more commonly in patients with the subacute subtype. [1][10]

Clinical featurestoggle arrow icon

Presentation is mostly nonspecific and clinicians should maintain a high index of suspicion in patients who acutely develop the following symptoms: [1][2][3]

In hyperacute liver failure, jaundice is usually minimal and the predominant presentation is encephalopathy, which can delay diagnosis and management.

Routinely consider ALF in patients presenting with acute encephalopathy.

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Managementtoggle arrow icon

Recommendations in this article are consistent with the 2011 update of the American Association for the Study of Liver Diseases (AASLD) position paper on the management of ALF. [3][12]

Approach [1][3][12]

The aim of initial management is metabolic and hemodynamic stability, which provides the best conditions for hepatic regeneration.

  • Unstable patients: Begin emergency stabilization (i.e., using the ABCDE approach) prior to diagnostic confirmation if severely ill upon presentation (see “Stabilization” for details).
  • Suspected ALF: Obtain liver chemistries, coagulation panel, and perform a detailed neurologic assessment.
  • Confirmed ALF: See “Diagnostics” and “Treatment” for details.
    • Identify liver transplant candidates early and refer them immediately to a transplant center if necessary.
    • Admit to a critical care unit. [13]
    • Begin aggressive supportive care: e.g., volume repletion, ICP monitoring, treatment of hypoglycemia and electrolyte disturbances.
    • Identify and treat the underlying cause.
    • Consider starting N-Acetylcysteine.
    • If the cause is medication- or substance-induced, notify the local poison control center.

The diagnosis of ALF requires the presence of hepatic injury (elevated aminotransferases), encephalopathy, and coagulopathy (INR > 1.5).

Acute liver failure can cause multiorgan dysfunction which requires system-based management in a critical care unit. [8]

Stabilization [1][3][12]

↑ ICP and severe hepatic encephalopathy account for 20–35% of mortality in patients with ALF. Early screening and treatment are essential to improve survival. [8][10]

Supportive care [1][3][12]

Diagnosticstoggle arrow icon

Diagnostic studies in ALF are used to confirm the diagnosis and assess the extent of associated organ failure. When the patient is stable, diagnostic studies also aid in the identification of the underlying cause if still unknown.

Laboratory studies [3][12]

Common findings include:

Imaging [19]

Imaging is not routinely indicated and may not provide any additional diagnostic information, but it is often part of the general diagnostic workup of acutely ill patients.

Do not mistake the nodular appearance of a regenerating necrotic liver for cirrhosis, as this may delay urgent management!

Identifying the underlying cause [12][15][20]

The etiology of ALF may be evident after taking the patient history (e.g., acetaminophen overdose), or it may require further investigation. In many cases, the etiology remains unknown even after an extensive evaluation. [1]

In ALF, the significant risks of performing a liver biopsy may outweigh the benefits, as most patients require a liver transplant regardless of biopsy results.

Treatmenttoggle arrow icon

Urgent liver transplantation remains the standard of care for ALF. [3]

Liver transplant [22]

Scoring systems

  • There are multiple methods available to predict which patients will likely require a liver transplant, and these are mostly based on clinical and laboratory parameters.
  • Commonly used scores
King's College criteria for risk stratification in acute liver failure [22]
ALF type Liver transplant indications
Secondary to acetaminophen toxicity
Other etiologies

Treatment of the underlying cause [10]

Specific measures may improve the prognosis when the cause of ALF is identified, for example:

N-acetylcysteine (NAC) [1][3]

  • Indicated in all patients with ALF due to confirmed or suspected acetaminophen toxicity.
  • Consider in patients with confirmed or suspected mushroom poisoning, e.g., Amanita phalloides.
  • Can be considered in patients with other causes of ALF (not routine). [1]
  • Dosage and administration
    • 21-hour IV NAC regimen
    • 72-hour oral NAC regimen
    • Consider extending therapy on a case-by-case basis depending on clinical and laboratory evaluations.

Administer N-acetylcysteine as early as possible if indicated, i.e., before hepatic encephalopathy becomes severe. [8]

Prognosistoggle arrow icon

Referencestoggle arrow icon

  1. 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): p.965-7.doi: 10.1002/hep.25551 . | Open in Read by QxMD
  2. AASLD Position Paper: The Management of Acute Liver Failure: Update 2011. Updated: September 1, 2011. Accessed: February 18, 2021.
  3. Bernal W, Wendon J. Acute Liver Failure. N Engl J Med. 2013; 369 (26): p.2525-2534.doi: 10.1056/nejmra1208937 . | Open in Read by QxMD
  4. Wibmer et al.. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv. 2021.
  5. Khan R, Koppe S. Modern Management of Acute Liver Failure. Gastroenterol Clin North Am. 2018; 47 (2): p.313-326.doi: 10.1016/j.gtc.2018.01.005 . | Open in Read by QxMD
  6. Bunchorntavakul C, Reddy KR. Acute Liver Failure.. Clin Liver Dis. 2017; 21 (4): p.769-792.doi: 10.1016/j.cld.2017.06.002 . | Open in Read by QxMD
  7. Wendon J, Cordoba J, Dhawan A, et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017; 66 (5): p.1047-1081.doi: 10.1016/j.jhep.2016.12.003 . | Open in Read by QxMD
  8. Patton H, Misel M, Gish RG. Acute liver failure in adults: an evidence-based management protocol for clinicians.. Gastroenterol Hepatol (N Y). 2012; 8 (3): p.161-212.
  9. Rovegno M, Vera M, Ruiz A, Benítez C. Current concepts in acute liver failure. Annals of Hepatology. 2019; 18 (4): p.543-552.doi: 10.1016/j.aohep.2019.04.008 . | Open in Read by QxMD
  10. Munoz SJ, Stravitz RT, Gabriel DA. Coagulopathy of acute liver failure.. Clin Liver Dis. 2009; 13 (1): p.95-107.doi: 10.1016/j.cld.2008.10.001 . | Open in Read by QxMD
  11. Pantanowitz L, Kruskall MS, Uhl L. Cryoprecipitate. Am J Clin Pathol. 2003; 119 (6): p.874-881.doi: 10.1309/56mqvqaqg8yu90x9 . | Open in Read by QxMD
  12. Scheiner B, Lindner G, Reiberger T, et al. Acid-base disorders in liver disease. J Hepatol. 2017; 67 (5): p.1062-1073.doi: 10.1016/j.jhep.2017.06.023 . | Open in Read by QxMD
  13. Romero M, Palmer SL, Kahn JA, et al. Imaging appearance in acute liver failure: correlation with clinical and pathology findings.. Dig Dis Sci. 2014; 59 (8): p.1987-95.doi: 10.1007/s10620-014-3106-6 . | Open in Read by QxMD
  14. Flamm SL, Yang Y-X, Singh S, et al. American Gastroenterological Association Institute Guidelines for the Diagnosis and Management of Acute Liver Failure. Gastroenterology. 2017; 152 (3): p.644-647.doi: 10.1053/j.gastro.2016.12.026 . | Open in Read by QxMD
  15. Eisenbach C. Diagnostic criteria for acute liver failure due to Wilson disease. World J Gastroenterol. 2007; 13 (11): p.1711.doi: 10.3748/wjg.v13.i11.1711 . | Open in Read by QxMD
  16. Castaldo ET, Chari RS. Liver transplantation for acute hepatic failure.. HPB : the official journal of the International Hepato Pancreato Biliary Association. 2006; 8 (1): p.29-34.doi: 10.1080/13651820500465741 . | Open in Read by QxMD
  17. Rosi S, Poretto V, Cavallin M, et al. Hepatic decompensation in the absence of obvious precipitants: the potential role of cytomegalovirus infection/reactivation. BMJ Open Gastroenterology. 2015; 2 (1): p.e000050.doi: 10.1136/bmjgast-2015-000050 . | Open in Read by QxMD
  18. Ichai P, Roque Afonso AM, Sebagh M, et al. Herpes simplex virus-associated acute liver failure: A difficult diagnosis with a poor prognosis. Liver Transpl. 2005; 11 (12): p.1550-1555.doi: 10.1002/lt.20545 . | Open in Read by QxMD
  19. Jalan R, Perricone G, Moreau R, Arroyo V, Williams R. Acute‐on‐Chronic Liver Failure: A New Disease or an Old One Hiding in Plain Sight?. Clin Liver Dis (Hoboken). 2020; 15 (S1).doi: 10.1002/cld.859 . | Open in Read by QxMD
  20. Perricone G, Jalan R. Acute‐on‐Chronic Liver Failure: A Distinct Clinical Syndrome That Has Reclassified Cirrhosis. Clinical Liver Disease. 2019; 14 (5): p.171-175.doi: 10.1002/cld.857 . | Open in Read by QxMD
  21. Sarin SK, Choudhury A, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatology International. 2019; 13 (4): p.353-390.doi: 10.1007/s12072-019-09946-3 . | Open in Read by QxMD
  22. Squires JE, McKiernan P, Squires RH. Acute Liver Failure: An Update.. Clin Liver Dis. 2018; 22 (4): p.773-805.doi: 10.1016/j.cld.2018.06.009 . | Open in Read by QxMD
  23. Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements.. Hepatology. 2017; 65 (1): p.363-373.doi: 10.1002/hep.28813 . | Open in Read by QxMD
  24. Rabinstein AA. Treatment of Brain Edema in Acute Liver Failure. Curr Treat Options Neurol. 2010; 12 (2): p.129-141.doi: 10.1007/s11940-010-0062-0 . | Open in Read by QxMD

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