Acute Liver Failure (ALF)

What is ALF?

ALF is defined as development of coagulopathy (INR>=1.5 or P time prolonged by 4-6 seconds or more) and any degree of mental alteration (encephalopathy) in a patient without pre-existing cirrhosis and with an illness of less than 26 weeks duration.

The original definition of acute/fulminant liver failure by Trey and Davidson in 1970 is still commonly used in UK.  It stipulates an onset of hepatic encephalopathy within 8 weeks of the first symptoms of illness, in patients without pre- existing liver disease

A number of other terms have been used including fulminant hepatic failure. Terms used signifying length of illness such as hyperacute (<7 days), acute (7-21 days) and subacute (>21 days and <26 weeks) are not particularly useful since they do not have prognostic significance.

How is ALF diagnosed?
The diagnosis is established in presence of coagulopathy or altered sensorium in any patient with moderate to severe hepatitis. Patients with ALF should preferably be managed in ITU.

Discuss the initial evaluation of ALF?

Careful history of possible exposures to viral infection and drugs or other toxins.

Physical examination- assess mental status, search for stigmata of chronic liver disease (to exclude acute on chronic liver disease), jaundice may be present, liver may be shrunk (due to massive hepatocyte loss) or enlarged early in viral hepatitis etc.

Investigations- to evaluate both the aetiology and severity of ALF

Severity- Liver biochemistry, P time, Urea and electrolytes, Mg, PO4, glucose, ABG, arterial lactate, FBC, arterial ammonia
Aetiology- paracetamol level, toxicology screen, viral hepatitis serologies ( anti- HAV IgM, HBsAg, anti-HBc, anti HEV), anti- HCV is also tested to recognise potential underlying infection, HIV tested for its implication in liver transplantation, caeruloplasmin levels, pregnancy test, autoimmune markers (ANA, SMA, Ig)

A liver biopsy may also be indicated when certain conditions such as autoimmune hepatitis, metastatic liver disease, lymphoma, or herpes simplex hepatitis are suspected.

Discuss important causes of ALF?

Paracetamol overdose
It is the leading cause of ALF in US and Europe and thus paracetamol levels should be checked in all patients with ALF. Very high aminotransferases (> 3500 IU/L) are highly correlated with paracetamol overdose and its possibility should be considered even when historic evidence is lacking.
NAC is recommended in any case of ALF in which acetaminophen overdose is a suspected or possible cause. NAC may still be of value 48 hours or more after ingestion.

Mushroom Poisoning (usually Amanita phalloides)
There is no available blood test to confirm the presence of these toxins, but this diagnosis should be suspected in patients with a history of severe GI symptoms
(nausea, vomiting, diarrhea, abdominal cramping), which occur within hours to a day of ingestion. Penicillin G and silibinin (silymarin or milk thistle) are the accepted antidotes. Patients should be listed for transplantation, as this procedure is often the only lifesaving option

Drug Induced Hepatotoxicity
Drugs other than paracetamol rarely cause dose-related toxicity. Most examples of idiosyncratic drug hepatotoxicity occur within the first 6 months after drug initiation. A potentially hepatotoxic medication that has been used continually for more than 1 to 2 years is unlikely to cause de novo liver damage.
Obtain details (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary
supplements taken over the past year

Viral Hepatitis
Hepatitis A, B and E can cause ALF. Hepatitis C alone does not appear to cause ALF. Herpes and varicella zoster virus infection can rarely cause ALF. Patients with known or suspected herpes virus or varicella zoster as the cause of acute liver failure should be treated with acyclovir.

Wilson disease
Early identification is critical because the fulminant presentation of Wilson disease is uniformly fatal without transplantation.
The disease typically occurs in young patients, accompanied by the abrupt onset of haemolytic anaemia with serum bilirubin levels >20 mg/dL. A high bilirubin
(mg/dL) to alkaline phosphatase (IU/L) ratio (>2.0) is a reliable albeit indirect indicator of Wilson disease in this setting. Other diagnostic tests include caeruloplasmin, serum and urinary copper levels slit lamp examination for Kayser-Fleischer rings and liver biopsy
Initiation of treatment with penicillamine is not recommended in
ALF as there is a risk of hypersensitivity to this agent.

Autoimmune hepatitis
Patients with acute liver failure due to autoimmune hepatitis should be treated with corticosteroids (prednisone, 40-60 mg/day).
Patients should be placed on the list for transplantation even while steroids are being administered

Acute Fatty Liver of Pregnancy/HELLP (Haemolysis, Elevated Liver Enzymes, Low Platelets) Syndrome

Consultation with obstetrical services and expeditious delivery is recommended

Discuss the management of ALF?

Treatment is mainly supportive.
Cerebral edema and intracranial hypertension (ICH) – most serious complications of ALF. Uncal herniation may occur and is uniformly fatal. The occurrence of cerebral edema and
ICH in ALF is related to severity of encephalopathy. Cerebral edema is seldom observed in patients with grade I-II encephalopathy. The risk of edema increases to 25% to 35% with progression to grade III, and 65% to 75% or more in patients reaching grade IV coma. A stepwise approach to management is therefore advised.

Grades I-II Encephalopathy

  • Consider referral to a transplant centre and listing for liver transplant
  • CT head to exclude other causes
  • Avoid sedation; small doses of short acting benzodiazepines may be used for unmanageable agitation.
  • Lactulose may be helpful

Grades III-IV Encephalopathy

  • Management as above plus
  • Intubation is advisable for airway protection.
  • Elevate head end of the bed (30 degrees).
  • Efforts should be made to avoid patient stimulation. Manoeuvres that cause straining or Valsalva-like movements in particular may increase ICP;
  • Seizures should be controlled with phenytoin and low dose benzodiazepines
  • Consider placement of intracranial pressure (ICP) monitoring device in transplant candidates to detect elevations in ICP so that interventions can be made to prevent herniation.
  • Mannitol is used for severe elevation of ICP or first clinical signs of herniation (decerebrate posturing, pupillary abnormalities).
  • Hyperventilation – it quickly lowers ICP via vasoconstriction causing decreased cerebral blood flow, but this effect is short-lived.


  • All patients with ALF are at risk for bacterial or fungal infection.
  • Prophylactic antibiotics are possibly helpful but not proven
  • Periodic surveillance cultures should be performed to detect bacterial and fungal infections as early as possible and prompt treatment should be initiated accordingly


  • Vitamin K- give at least one dose
  • FFP- only in the setting of haemorrhage or prior to invasive procedures
  • Platelet-give for platelet counts < 10,000/mm3 or for invasive procedures

Gastrointestinal Bleeding

Prophylaxis for stress ulceration- H2 blocking agents or PPIs (or sucralfate as a second-line agent)

Haemodynamic/Renal Failure

  • Acute renal failure is a frequent complication and may be due to dehydration, hepatorenal syndrome or acute tubular necrosis
  • Volume replacement
  • Pressor support as needed to maintain MAP
  • Continuous mode of haemodialysis if needed
  • Vasopressin- not useful in ALF: potentially harmful


  • Monitor closely- glucose, K, Mg, PO4
  • Consider nutrition- enteral feedings if possible, otherwise TPN

Discuss the prognosis of ALF?

Spontaneous survival rates without transplant are around 40%. Post transplant
survival rates for ALF have been reported to be as high as 80% to 90%.
Urgent hepatic transplantation is indicated in acute liver failure where prognostic indicators suggest a high likelihood of death. However, currently available prognostic scoring systems do not adequately predict outcome and determine candidacy for liver transplantation.


  1. AASLD Position Paper: The Management of Acute Liver Failure (archived copy at Webcite)

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