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. 
- Chronic liver disease (CLD): a condition characterized by progressive deterioration of hepatic function over at least 26–28 weeks (∼ 6 months), e.g., cirrhosis. 
- 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. 
- Acute-on-chronic liver failure (ACLF): A distinct syndrome involving acute decompensation of CLD accompanied by and significant short-term mortality. 
|Etiology of acute liver failure |
|Hepatotoxic medications|| |
|Other exogenous toxins|
Presentation is mostly nonspecific and clinicians should maintain a high index of suspicion in patients who acutely develop the following symptoms: 
- (e.g., altered level of consciousness, asterixis )
- Nausea, vomiting
- Fatigue, lethargy, malaise
- Jaundice, pruritus
- Abdominal pain: may be located in the RUQ or diffuse, secondary to ascites
- Features of the underlying etiology (e.g., Kayser-Fleischer rings in Wilson disease)
Routinely consider ALF in patients presenting with acute encephalopathy.
- Severe acute hepatitis without liver failure
- Chronic liver disease with superimposed illness
- Other encephalitis or encephalopathy, e.g., drugs and toxins, uremic encephalopathy (See “Altered mental status and coma.”)
- See also “Jaundice and cholestasis.”
The differential diagnoses listed here are not exhaustive.
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 ) 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. 
- 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.
- perfusion early to avoid or reduce organ damage. : Restore volume and
- Respiratory support
Management of encephalopathy and increased ICP: 
- Consider early intubation.
- Refer early for liver transplantation.
- Control hyperammonemia: Consider lactulose . 
- Begin and as needed.
- Monitoring: Assess clinical signs of encephalopathy and ammonia levels.
- Consider intracranial pressure monitoring only in patients with .
hepatic encephalopathy account for 20–35% of mortality in patients with ALF. Early screening and treatment are essential to improve survival.  and severe
Supportive care 
- Metabolic and nutritional support
- Correct coagulopathy if there is active bleeding or need for invasive procedures, usually using a combination of: 
- Consider GI bleeding. to prevent
- Consult hematology for specialized management.
- Monitor coagulation studies and consider using viscoelastic hemostatic assays.
- Management of kidney injury
- Infection control: patients with ALF are at increased risk of sepsis.
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 
Common findings include:
- CBC: : typically platelet count ≤ 150,000/mm3; other findings are variable and depend on the underlying etiology.
- Liver chemistries
- Coagulation panel
- ABG or VBG : Findings vary depending on the underlying etiology (see “Acid-base disorders” for more information). 
- Serum ammonia (preferably arterial): frequently elevated; values > 150 micromol/L are associated with a higher risk of increased ICP.
- LDH: typically elevated in early stages of acute liver injury
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.
Abdominal imaging: Findings vary as ALF progresses.
- Early findings
- Abdominal x-ray: may show hepatomegaly
- Abdominal ultrasound: liver echogenicity may be heterogeneously decreased (usually a sign of necrosis); possible presence of ascites
- Doppler ultrasound: can be useful to identify the underlying cause (e.g., portal vein thrombosis, hepatic ischemia)
- CT/MRI abdomen with contrast: usually shows diffuse enhancement (e.g., in necrosis), may show ascites and/or hepatomegaly
- Findings in late stages: In patients who have been sick for at least seven days, ultrasound, CT, or MRI may show a nodular surface, which can be mistaken for cirrhosis.
- Early findings
- Additional imaging: Consider CT head to rule out other .
Identifying the underlying cause 
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. 
- Screen the following viral serologies in all patients: hepatitis A (IgM), hepatitis B (surface antigen and core IgM), hepatitis C (antibodies), and hepatitis E (IgG and possibly RNA testing)
- Toxicology screen: measure acetaminophen levels and consider screening for other measurable phenytoin, e.g., .
- Consider testing for more uncommon etiologies based on clinical suspicion.
- Hematologic studies (e.g., blood smear, Coombs test) may show abnormalities, e.g., hemolytic anemia in Wilson disease. 
Liver biopsy 
- Findings: specific to each underlying etiology; necrosis and regeneration are commonly seen.
- Complications: significant risk of bleeding
Urgent liver transplantation remains the standard of care for ALF. 
Liver transplant 
- Consider liver transplant in most patients, as a high proportion do not recover with supportive therapy alone (see “Prognosis”).
- Use prognostic scoring systems (e.g., stratify patients' need and urgency of transplantation. , ) to risk-
- Consult the transplant team early and, if necessary, transfer candidates to a transplant center without delay.
- Treat any complications arising during the waiting period, e.g., cerebral edema, acute kidney injury, sepsis, coagulopathy (see “Management”).
- 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 |
|ALF type||Liver transplant indications|
|Secondary to acetaminophen toxicity|
Treatment of the underlying cause 
Specific measures may improve the prognosis when the cause of ALF is identified, for example:
- : Consider a trial of steroids on a case-by-case basis, weighing the increased risk of infection against the likely benefit.
- Viral hepatitis: Certain antivirals (e.g., for hepatitis B) can improve the prognosis.
- Pregnancy-related liver disease: Urgent delivery of the fetus is indicated.
- Acetaminophen toxicity: Treat with N-acetylcysteine.
N-acetylcysteine (NAC) 
- Indicated in all patients with ALF due to confirmed or suspected .
- Consider in patients with confirmed or suspected mushroom poisoning, e.g., .
- Can be considered in patients with other causes of ALF (not routine). 
- Dosage and administration
- Advances in management have improved outcomes for ALF patients, but prognosis remains poor (overall mortality of 30–40%) and is worse for ALF of indeterminate etiology. .
- Survival without liver transplant depends on etiology 
- Survival with liver transplant: ∼ 65–84% at 1 year