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Acute liver failure

Last updated: October 8, 2021

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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.

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

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

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.

The differential diagnoses listed here are not exhaustive.

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]

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.

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]

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