Acute liver failure

Question 1

What is acute liver failure?

Answer 1

Jaundice, encephalopathy, coagulopathy.

O’Grady classification (time from jaundice to encephalopathy):
Hyperacute - 1 week
Acute - 1 month
Subacute - 3 months

Question 2

What are the causes of acute liver failure?

Answer 2

Infective: EBV, HCV, HBV, leptospirosis
Neoplastic: HCC, or secondaries
Vascular: Budd-Chiari, veno-occulusive disease
Inflammatory/immune: PBC, Sclerosing cholangitis, Autoimmune
Transplant failure
Extras: Pregnancy (HELLP, acute fatty liver)
Drugs: Paracetamol, chemotherapy

Question 3

What is the mechanism of paracetamol overdose toxicity?

Answer 3

Paracetamol is 90% metabolised by glucuronidation and sulphation.
10% metabolised by CYP450 enzymes, the product of which is NAPQI.
NAPQI is normally metabolised to non-toxic metabolites by glutathione.
Glutathione reserves get overwhelmed in paracetamol overdose leading to build up hepatotoxic and nephrotoxic metabolites.

Question 4

How can you score severity of acute liver failure?

Answer 4

Child Pugh score is used for prognositic purposes. Graded A, B, C and indicates likelihood of mortality.
Comprises:
- Albumin
- Bilirubin
- Coagulopathy (INR)
- Ascites
- Encephalopathy

King’s criteria:
- Used for referral for transplant in paracetamol and non-paracetamol acute liver failure.

- Paracetamol:
pH <7.3
or all of:
i) Creatinine >300
ii) INR >6.5
iii) Grade 3 encephalopathy (West Haven criteria)

- Non-paracetamol:
INR >6.5 
or 3 of:
i) Bili >300
ii) INR >3.5
iii)Age <10 or >40
iv) Non-viral cause
v) Non hyperacute

MELD predicts 3 month mortality and prioritisation for transplant.