Acute Liver Failure
On this page
Direct answer
Acute liver failure is severe hepatocellular injury with coagulopathy (INR 1.5 or more) and encephalopathy developing within 26 weeks of the first symptom in a patient without prior cirrhosis — memorise that sentence, because FMGE stems are built around it. In India the leading causes are viral hepatitis A and E, antituberculosis drugs and paracetamol, a mirror image of Western paracetamol-dominated series, and hepatitis E in the third trimester of pregnancy carries a notoriously high case fatality. Tempo predicts outcome: O'Grady's hyperacute variety (encephalopathy within 7 days of jaundice) paradoxically carries the best survival, subacute (over weeks) the worst. Management is intensive-organ support, N-acetylcysteine, infection surveillance, cerebral oedema control and early transplant referral decided on King's College criteria.
What you must remember
- Definition numbers: INR 1.5 or above plus any grade of encephalopathy within 26 weeks, no known cirrhosis; encephalopathy is graded I (mild confusion, sleep reversal) to IV (unresponsive), and grade drives airway protection.
- Indian cause ladder: hepatitis E and A lead, followed by antituberculosis therapy (isoniazid, rifampicin), paracetamol, hepatitis B flare and Wilson disease in patients under 30.
- King's College criteria, paracetamol: arterial pH below 7.30 after resuscitation, OR all three of INR above 6.5, creatinine above 3.4 mg/dL and grade III-IV encephalopathy.
- King's College criteria, non-paracetamol: INR above 6.5 alone, or any three of age under 10 or over 40, unfavourable aetiology, jaundice-to-encephalopathy interval over 7 days, INR above 3.5, bilirubin above 17.5 mg/dL.
- Cerebral oedema: the dominant cause of death; nurse head-up 30 degrees, avoid hyponatraemia and hypercapnia, mannitol 0.5-1 g/kg when serum osmolality permits.
- N-acetylcysteine: 150 mg/kg over the first hour, then 50 mg/kg over 4 hours and 100 mg/kg over 16 hours; most effective within 8-10 hours of ingestion, and used beyond paracetamol in many units for non-paracetamol failure.
- Wilsonian failure pattern: Coombs-negative haemolysis, low urate, alkaline phosphatase-to-bilirubin ratio below 4, Kayser-Fleischer rings — refer for transplant listing immediately.
- Supportive rules: treat infection empirically and culture everything, avoid sedatives and nephrotoxins, feed early (protein restriction is obsolete), and use fresh frozen plasma only for bleeding or procedures, not for the number alone.
A night in the liver unit
A 24-year-old woman in the third trimester reaches the emergency department with five days of jaundice and now drowsiness. INR is 3.4, bilirubin 18 mg/dL, creatinine 1.6 mg/dL, glucose 58 mg/dL, and hepatitis E IgM is positive. Walk the pathway in order: this is hyperacute failure, so the airway is assessed first because grade II encephalopathy can progress within hours. She is nursed head-up, started on dextrose infusion for the hypoglycaemia, given vitamin K (synthesis is impaired, and it costs nothing), and N-acetylcysteine is begun on the safety-first logic many Indian units follow. Arterial ammonia is sent — a level above 200 micromol/L flags poor outcome. The obstetric team is involved early: delivery decisions balance hepatic recovery against foetal viability, and this is one situation where the mother's mortality risk is quoted in double digits.
Contrast a staggered paracetamol ingestion in a young man: 12 hours after the last dose his pH is 7.26 and lactate is 8 mmol/L. A single pH value below 7.30 already meets King's College criteria for paracetamol failure — no arithmetic with three variables needed — so transplant conversations start that night, not after the INR climbs. That asymmetry between the two criteria sets, one single-variable and one three-variable, is exactly the discrimination the exam tests.
Where the exam probes
NBE rarely asks "what is acute liver failure"; it gives an INR, a time interval and a cause, then asks which criterion or which complication. Expect stems on the jaundice-to-encephalopathy interval (hyperacute versus subacute), on cerebral oedema as the leading killer with hyponatraemia as the aggravator, and on the Indian aetiology twist — a pregnant woman from an epidemic belt is hepatitis E until proven otherwise, a patient on antituberculosis therapy who turns icteric has drug-induced failure until the INR pattern says otherwise. The trap question is fresh frozen plasma given to normalise a number: the correct answer is that coagulopathy defines severity and is not corrected prophylactically. Viva examiners also love why paracetamol antidote timing matters and why grade IV encephalopathy means elective intubation.
Frequently asked questions
What INR and time window define acute liver failure?
INR of 1.5 or more with encephalopathy within 26 weeks of symptom onset in a patient without cirrhosis or pre-existing liver disease.
Which cause of acute liver failure is deadliest in Indian pregnancy?
Hepatitis E, particularly in the third trimester, with case fatality substantially higher than in non-pregnant patients.
What is the most common cause of death in acute liver failure?
Cerebral oedema with intracranial hypertension, followed closely by sepsis and multi-organ failure.
When is N-acetylcysteine most effective in paracetamol overdose?
Within 8-10 hours of ingestion, although it is still given beyond that window and is not withheld once the patient presents.
What are the King's College criteria in paracetamol-induced failure?
Arterial pH below 7.30 after resuscitation, or the combination of INR above 6.5, creatinine above 3.4 mg/dL and grade III-IV encephalopathy.