Summary
Definition
History and exam
Key diagnostic factors
- hepatotoxic medication
- chronic alcohol misuse
- pregnancy
- jaundice
- signs of hepatic encephalopathy
Other diagnostic factors
- absence of history of chronic liver disease
- abdominal pain
- nausea
- vomiting
- malaise
- signs of cerebral edema
- right upper quadrant tenderness
- hepatomegaly
- 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 behaviors
- absence of malignancy
Risk factors
- chronic alcohol misuse
- poor nutritional status or fasting
- female sex
- age >40 years
- pregnancy
- chronic hepatitis B
- chronic pain and narcotic use
- herbal and dietary supplement hepatotoxicity
- acetaminophen and antidepressant therapy
- chronic hepatitis C
- HIV and hepatitis C coinfection
Diagnostic investigations
1st investigations to order
- liver function tests
- prothrombin time/INR
- basic metabolic panel
- CBC
- blood type and screen
- serum amylase and lipase
- arterial blood gas
- arterial blood lactate
- acetaminophen 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 ophthalmologic examination
- arterial ammonia
- HIV test
- urinalysis and urine sodium
- surveillance cultures
- Coombs test
- liver biopsy
- CT scan of head
- CT/MR cholangiography
- Transcranial Doppler
Treatment algorithm
all patients
Contributors
Authors
Stevan A. Gonzalez, MD, MS

Associate Professor
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
Fort Worth
TX
Disclosures
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.
Acknowledgements
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.
Disclosures
EBK declared that he had no competing interests.
Peer reviewers
Timothy J. Davern, MD
Director of Acute Liver Failure Program
California Pacific Medical Center Liver Transplant Program
San Francisco
CA
Disclosures
Not disclosed.
Muhammad Dawwas, MRCP
Specialist Registrar
Liver Unit
Addenbrooke's Hospital
Cambridge
UK
Disclosures
Not disclosed.
Differentials
- Severe acute hepatitis
- Cholestasis
- Hemolysis
More DifferentialsGuidelines
- Acute-on-chronic liver failure clinical guidelines
- AASLD practice guidance on drug, herbal and dietary supplement-induced liver injury
More GuidelinesPatient leaflets
Acute liver failure
Hepatitis B: should I have the vaccine?
More Patient leafletsVideos
Tracheal intubation: animated demonstration
Bag-valve-mask ventilation: animated demonstration
More videosLog in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer