A 43-year-old female with a history of paranoid schizophrenia and multiple episodes of selfharm, presented to the Emergency Department with decreased conscious state. She had been seen three days earlier for possible worsening of her psychosis and discharged home.
Her haematology and biochemistry results at both presentations are as follows:
| Parameter | Patient Value | Normal Adult Range | |
| 1st Presentation | 2nd Presentation | ||
| Haemoglobin | 134 g/L | 135 g/L | 115 – 160 |
| White cell count | 12.6 x 109 /L* | 7.5 x 109/L | 4.0 – 11.0 |
| Platelet count | 250 x 1012/L | 76 x 1012/L* | 150 – 400 |
| Prothrombin time | 40.0 seconds* | 12.3 – 16.6 | |
| International Normalised Ratio (INR) | 4.1* | 0.9 – 1.3 | |
| Activated partial thromboplastin time (APTT) | 35.0 seconds | 27.0 – 38.5 | |
| Fibrinogen | 1.8 g/L* | 2.0 – 4.0 | |
| Sodium | 139 mmol/L | 136 mmol/L | 134 – 146 |
| Potassium | 3.6 mmol/L | 4.6 mmol/L | 3.4 – 5.0 |
| Bicarbonate | 18 mmol/L* | 21 mmol/L* | 22 – 32 |
| Urea | 5.0 mmol/L | 18.9 mmol/L* | 3.0 – 8.0 |
| Creatinine | 56 µmol/L | 448 µmol/L* | 45 – 90 |
| Bilirubin total | 6.0 µmol/L | 81 µmol/L* | < 20 |
| Alanine aminotransferase (ALT) | 31 U/L | 11700 U/L* | < 35 |
| Alkaline phosphatase (ALP) | 88 U/L | 245 U/L* | 35 – 135 |
| Gamma glutamyl transferase (GGT) | 13 U/L | 104 U/L* | < 40 |
| Lactate | 4 mmol/L | < 1.5 | |
| Paracetamol | < 10 mg/L | 10 mg/L | |
| Urine Ethanol | Not detected | ||
| Urine Amphetamines | Not detected | ||
| Urine Benzodiazepines | Detected | ||
| Urine Cannabinoids | Not detected | ||
| Urine Opiates | Not detected | ||
a) What is the underlying diagnosis?
b) List the possible causes in this patient.
c) Outline your immediate management.
a) What is the underlying diagnosis?
Hyperacute (fulminant) hepatic failure
b) List the possible causes in this patient.
Paracetamol
Idiosyncratic drug reaction
Other toxin e.g. Amanita phalloides
Viral (hepatitis A and E as hyperacute consider B, CMV, Epstein Barr)
Ischaemic hepatitis
Budd-Chiari
c) Outline your immediate management.
Concurrent resuscitation and institution of supportive care and monitoring with focussed assessment
to identify underlying cause and definitive management as indicated.
Airway management and oxygen – likely to need intubation and mechanical ventilation with
ARDSNet targets and PCO2 32-38 mmHg
Haemodynamic support for adequate MAP and CPP >60 and appropriate monitoring (A-line,
PAC/PiCCO, bedside echo etc.). Avoid fluid overload
Strategies to offset cerebral oedema (head-up, neutral position, sedation, PCO2 targets, Na 145-155
etc.)
ICP monitoring controversial
Consider renal replacement therapy
Extracorporeal albumin dialysis therapies (SPAD, MARS and Prometheus) have limited evidence to
support use
Monitoring of coagulopathy using TEG/ROTEM to guide correction. Correction to cover invasive
procedures or if bleeding otherwise not.
Monitor blood glucose
Screening for infection and antibiotics as indicated +/- empiric broad spectrum cover including antifungal
Stress ulcer prophylaxis
Nutrition
Specific
NAC
Lactulose / Neomycin / Rifaximin controversial and use varies from unit to unit
Investigations including liver USS, viral screen
Discussion with liver transplant team / transfer to ICU with liver unit (does not currently meet
transplantation criteria)
The diagnosis is clearly liver failure. The college further qualify their description as "fulminant". That term is very 1990s. What makes a liver failure fulminate? Well, apparently that just means it is acute (see Sass et al, 2005). The term was originally applied to patients in whom encephalopathy developed within two weeks of the development of jaundice. These days, the terminology we use is hyparcute (0-7 days), acute (8-28 days) and subacute (29 days to 8 weeks). The disorders were redefined by Williams et al in 1993, on the basis of the fact that they correlate better with survival statistics (paradoxically, the hyperacute ones do much better).
Possible categories of the causes:
|
Vascular:
Infectious:
Neoplastic:
Drug-induced:
|
Idiopathic: idiosyncratic drug reactions:
Congenital:
Autoimmune:
Traumatic:
Endocrine/metabolic:
|
Of these, the following short list is relevant. However, it must be added that the college did not specify how many differentials they wanted. You could have brought up your various azathiprine-induced hepatitis and Amanita phalloides mushrooms.
Thus:
Management
As with most things, management falls into the category of specific management and supportive management. Specific management may be viewed as a series of antidotes or proven solutions tailored to specific causes of the liver failure.
| Paracetamol overdose |
N-acetylcystine |
| Wilson's disease (chronic) |
Copper chelating agents |
| Hepatic vein thrombosis |
Thrombolysis / clot retrieval; TIPS procedure |
| Hepatitis viruses |
Antiviral drugs |
| Autoimmune hepatitis |
Steroids may be helpful... or may be harmful. |
| Alcoholic hepatitis |
Steroids are probably helpful |
| Valproate overdose |
L-carnitine, and probably also dialysis to extract the excess ammonia |
| Amanita phalloides |
Haemopherfusion may remove the phallotoxins |
A discussion of supportive management might take the following shape:
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