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.
Idiopathic: idiosyncratic drug reactions:
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)
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
- 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.
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.
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.