Acute liver failure: causes and diagnostic evaluation

Acute liver failure has a limited number of of causes. It is either toxins, ischaemia, sepsis, or viruses. And of the toxins, it is very often paracetamol. Weirder differentials may be presented in a question which does not specify how many differentials to provide; but if one is limited to (say) six, one should not bring up Amanita phalloides at the top.


The college love acute liver disease. It is typically presented as a "what caused this horrific LFT picture and this coma in a schizophrenic pregnant drug-using immunology patient". The following questions have been asked:

  • Question 3.1 from the second paper of 2015 (list of six differentials)
  • Question 14 from the second paper of 2014 (broad list of differentials; acute management)
  • Question 30 from the second paper of 2010 (list of five differentials; acute complications)

Definition of liver failure

The various types of acute hepatic failure are divided into chronological niches:

Hyperacute hepatic failure: 0-7 days

These people collapse suddenly, and (aetiology permitting) they also bounce back rather rapidly. Typically this sort of hepatic failure presents with severe encephalopathy coagulopathy, and raised intracranial pressure. The LFTs tend to be ridiculously deranged.

The major causes in the developed world are paracetamol and hepatitis A or B.

Acute hepatic failure: 8-28 days

These people collapse gradually over about a week.

The typical causes include hepatitis viruses and idiosyncratic drug reactions

Subacute hepatic failure: 29 days - 8 weeks

This form of hepatic dyfunction creeps up on you gradually, and carries with it the poorest chance of meaningful recovery. This includes the frustrating "seronegative hepatitis" group, who have no positive tests but who behave like a viral hepatitis. The LFTs in this group are usually the least impressive.

Differential diagnosis for the aetiology of acute hepatic failure

In order to render this massive list more memorable, I have first attempted to pidgeonhole the aetiologies into the familiar VINDICATE matrix of differentials.


  • Right heart failure
  • Hepatic arterial ischaemia (eg. due to either global ischaemia, or due to an embolic event)
  • Hepatic venous insufficiency (Budd-Chiari syndrome)
  • Veno-occlusive disease (eg. post bone marrow transplant)


  • Hepatitis A, B and C
  • Hepres simlex
  • Cytomegalovirus
  • Varicella


  • Colonic carcinoma metastases
  • Hepatocellular carcinoma
  • Lymphoma


  • Paracetamol
  • Alcohol
  • Kava-kava
  • Tuberculosis antibiotics
  • Amanita phalloides mushroom
  • Cocaine (by ischaemia)
  • Solvents: xylene, chloroform, trichloroethylene, carbon tetrachloride
  • MDMA

Idiopathic: idiosyncratic drug reactions:

  • Anticonvulsants
  • NSAIDs
  • Aspirin in children (Reye's syndrome)


  • Wilson's disease


  • Haemophagocytic syndrome
  • Vasculitic hepatitis


  • Crush injury to the liver
  • Capsular hematoma
  • Disruption of hepatic vessels
  • Hyperthermia-induced liver injury


  • Acute fatty liver of pregnancy
  • HELLP syndrome
  • Pregnancy-associated liver rupture

Diagnostic blood work

Perhaps some basic LFTs will be in order. What these may mean is discussed in the chapter on interpretation of deranged LFTs

In addition, one may wish to order something more specific:

Hyperacute and acute hepatic failure:

FBC for the eosinophil count (sometimes elevated in autoimmune hepatitis, and will likely be elevated in hepatitis due to some sort of idiosyncratic drug allergy)

Paracetamol level

LDH which is usually elevated in malignancy

CK and urinary myoglobin which will be elevated in hyperthermic injuries

Hepatitis A investigations: Anti-HAV, Hep A IGM

Hepatitis B investigations: Hep B core antibodies, surfance antigen, and Hep B DNA

Of the hepatitis viruses, A and C dont tend to cause acute liver failure.

It is mainly Hep B. One achieves the diagnosis of acute Hep B hepatitis by finding an IgM antibody to the Hep B core antigen. The surface antibody has long gone by the time the bloated yellow patient presents to hospital.

Hepatic failure in the pregnant patient

Uric acid which is elevated in fatty liver of pregnancy

FBC for...

  • neutrophilia (this tends to happen in acute fatty liver of pregnancy)
  • thrombocytopenia (this is part of the HELLP diagnosis)

Coags for DIC which forms part of HELLP syndrome

A screen for the unusual causes of hepatitis

Urinary copper which is elevated in Wilson's disease

Ceruloplasmin which is abnormally low in Wilson's disease

  • Wilsons's disease will usually also have cirrhosis and non-immune hemolysis

EBV serology - in the immunocompromised host

CMV serology - in the immunocompromised host

HSV serology - in the immunocompromised host

Varicella serology - in the immunocompromised host

Dengue fever serology

Yellow fever serology

Anti-SSM: smooth muscle antibodies, which are positive in autimmune hepatitis.

Diagnostic imaging


To rule out right heart failure, a TTE should be performed.

This tends to become very important whe one is considered for transplantation.

They wont let you kill your nice new liver with your faulty old right ventricle.


A Doppler will assess the flows in the hepatic vessels, and rule out the vascular causes of acute failure. Additionally, one may be able to see hematomae and liver rupture in pregnancy, and one may be able to comment on the stone content of the gallbladder and the diameter of the common bile duct.

CT abdomen with IV contrast:

Metastatic deposits will be seen on CT. It will provide a lot of additional information regarding the abdominal organs, eg. wheter massive splenomegaly is present, whether the abdomen is full of lymph nodes, and whether there is liver rupture.

Liver biopsy:

In acute hepatic necrosis, you very rarely get any useful information from this (as it will always come back as "acute necrosis" rather than anything diagnostic). One might be lucky enough to catch some tumour cells or something staining positive on immunofluorescence (eg. in autoimmune hepatitis). Generally speaking, CT-guided or transjugular biopsy are the safest methods.


Chapter 44   (pp. 501) Liver  failure by Christopher  Willars  and  Julia  Wendon

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