Last reviewed: 23 Dec 2021
Last updated: 29 May 2020



History and exam

Key diagnostic factors

  • presence of risk factors
  • hepatotoxic medication
  • jaundice
  • signs of hepatic encephalopathy

Other diagnostic factors

  • absence of history of chronic liver disease
  • abdominal pain
  • nausea
  • vomiting
  • malaise
  • signs of cerebral oedema
  • 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 abuse and high-risk behaviours

Risk factors

  • chronic alcohol abuse
  • poor nutritional status
  • female sex
  • age >40 years
  • pregnancy
  • chronic hepatitis B
  • chronic pain and narcotic use
  • complementary and alternative medicine hepatotoxicity
  • paracetamol and antidepressant therapy
  • chronic hepatitis C
  • HIV and hepatitis C co-infection

Diagnostic investigations

1st investigations to order

  • liver function tests
  • prothrombin time/INR
  • basic metabolic panel
  • FBC
  • blood type and screen
  • arterial blood gas
  • arterial blood lactate
  • paracetamol level
  • urine toxicology screen
  • factor V level
  • viral hepatitis serologies
  • autoimmune hepatitis markers
  • pregnancy test
  • chest x-ray
  • abdominal ultrasound with Doppler

Investigations to consider

  • 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

Treatment algorithm



Stevan A. Gonzalez, MD, MS
Stevan A. Gonzalez

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



SAG declares that he has no competing interests.


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.

Peer reviewers

Timothy J. Davern, MD

Director of Acute Liver Failure Program

California Pacific Medical Center Liver Transplant Program

San Francisco



Not disclosed.

Muhammad Dawwas, MRCP

Specialist Registrar

Liver Unit

Addenbrooke's Hospital




Not disclosed.

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