Acute liver failure is a rare disease defined by jaundice, coagulopathy, and hepatic encephalopathy.
The aetiology and the interval from onset of jaundice to the development of encephalopathy have a significant impact on prognosis.
Aetiology is established by history, serological assays, and exclusion of alternative causes, including acute presentations of chronic liver diseases.
Treatment involves intensive care unit monitoring, specific therapies based on aetiology, and management of known complications.
All patients should be considered for possible liver transplantation.
Prognostic models may be used to assess the probability of spontaneous recovery and are instrumental in selection of patients who should potentially undergo liver transplantation.
Acute liver failure (ALF) is a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease.
If these symptoms occur in a patient with pre-existing liver disease, the term acute-on-chronic liver failure is used.
ALF may be classified as hyperacute, acute, or subacute, depending on the interval from the onset of jaundice to the development of encephalopathy.
The term acute liver failure is preferred over fulminant hepatic failure or acute hepatic necrosis, although these terms have been used historically to classify hepatic failure.
History and exam
Key diagnostic factors
- presence of risk factors
- hepatotoxic medication
- chronic alcohol misuse
- signs of hepatic encephalopathy
Other diagnostic factors
- absence of history of chronic liver disease
- abdominal pain
- signs of cerebral oedema
- right upper quadrant tenderness
- absence of splenomegaly
- absence of spider angiomata
- absence of palmar erythema
- absence of ascites
- depression or suicidal ideation
- exposure to hepatotoxins
- illicit drug misuse and high-risk behaviours
- absence of malignancy
- chronic alcohol misuse
- poor nutritional status or fasting
- female sex
- age >40 years
- chronic hepatitis B
- chronic pain and narcotic use
- herbal and dietary supplement hepatotoxicity
- paracetamol and antidepressant therapy
- chronic hepatitis C
- HIV and hepatitis C co-infection
1st investigations to order
- liver function tests
- prothrombin time/INR
- basic metabolic panel
- blood type and screen
- serum amylase and lipase
- arterial blood gas
- arterial blood lactate
- paracetamol level
- urine toxicology screen
- viral hepatitis serologies
- autoimmune hepatitis markers
- pregnancy test
- chest x-ray
- abdominal ultrasound with Doppler
Investigations to consider
- factor V level
- viral hepatitis polymerase chain reaction (PCR) studies
- serum ceruloplasmin
- serum copper
- 24-hour urinary copper excretion
- slit-lamp ophthalmological examination
- arterial ammonia
- HIV test
- urinalysis and urine sodium
- surveillance cultures
- Coombs test
- liver biopsy
- CT scan of head
- CT/MR cholangiography
- Transcranial Doppler
Stevan A. Gonzalez, MD, MS
Department of Internal Medicine
TCU and UNTHSC School of Medicine
Medical Director of Liver Transplantation
Annette C. and Harold C. Simmons Transplant Institute
Baylor All Saints Medical Center
SG has received honoraria from Mallinckrodt Pharmaceuticals for consulting work and from Salix Pharmaceuticals for speaker’s bureau and consulting work. SG has previously received honoraria from Intercept Pharmaceuticals for advisory activities.
Dr Stevan Gonzalez would like to gratefully acknowledge the late Dr Emmet B. Keeffe who previously co-contributed to this topic; an esteemed colleague, friend, and mentor.
EBK declared that he had no competing interests.
Timothy J. Davern, MD
Director of Acute Liver Failure Program
California Pacific Medical Center Liver Transplant Program
Muhammad Dawwas, MRCP
- Severe acute hepatitis
- Acute-on-chronic liver failure clinical guidelines
- AASLD practice guidance on drug, herbal and dietary supplement-induced liver injury
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