Acute Liver Failure — Written Clinical Reasoning

SAQ 1 — Wilson disease acute liver failure in a young woman (20 marks, 30 minutes)

Prompt: Outline your immediate assessment, the aetiological workup, your integrated management plan addressing each problem, and the communication framework. Justify each decision with reference to evidence. [1]

Model Answer

Problem list (4 marks): [1]

1. Wilson disease acute liver failure — grade 2 encephalopathy with INR 3.8, the defining criteria met; confirmed by the pathognomonic combination of Coombs-negative haemolytic anaemia (haemoglobin 72, reticulocytes 8 per cent, negative Coombs), a low alkaline phosphatase (35, counterintuitively low for the degree of liver injury), a low caeruloplasmin (0.08 g/L) and a high 24-hour urinary copper (480 micrograms).
2. Grade 2 encephalopathy with the risk of progression to cerebral oedema — the leading cause of death in ALF, complicating up to 80 percent of grade 4 encephalopathy.
3. Coagulopathy (INR 3.8) — a prognostic marker and a King's College Criterion; must not be routinely corrected.
4. Coombs-negative haemolytic anaemia (haemoglobin 72) — the released copper is damaging red cell membranes.
5. The genetic and family implications — Wilson disease is autosomal recessive; siblings require screening. [1]

Step 1 — Immediate actions and the cause-specific diagnosis (5 marks): [1]

The most urgent action is to recognise that this is Wilson disease ALF and refer for urgent liver transplant — the medical mortality approaches 100 percent and transplant is the only cure. The diagnosis is confirmed by the classic triad: Coombs-negative haemolytic anaemia, low ALP (the ALP-to-bilirubin ratio is below 2, a validated discriminator), and low caeruloplasmin with high urinary copper. I would confirm Kayser-Fleischer rings on slit-lamp examination. The key exam point: Wilson disease is the cause of ALF that every physician must spot, because it changes the management entirely — the patient will not survive without transplant. [1]

In parallel I would admit her to the liver ICU, secure the airway if encephalopathy deepens, establish arterial and central access, monitor the GCS and pupils hourly, correct the hypoglycaemia with 10 per cent dextrose (hypoglycaemia is both a complication and a poor prognostic sign), and start the 21-hour intravenous N-acetylcysteine regimen empirically (150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours) because NAC has a transplant-free survival benefit in early-stage non-acetaminophen ALF [5].

Step 2 — The aetiological workup (3 marks): [1]

I would confirm the cause and exclude alternatives. The full panel: paracetamol level (even if denied), viral serology (HBsAg, anti-HBc IgM, anti-HAV IgM, anti-HEV IgM, HSV and EBV PCR), autoimmune markers (ANA, SMA, anti-LKM, IgG), a pregnancy test, a drug and herbal history, and a Doppler ultrasound of the hepatic vessels to exclude Budd-Chiari. For Wilson disease specifically, I would send a caeruloplasmin (low), a 24-hour urinary copper (high), and arrange slit-lamp examination for Kayser-Fleischer rings. A liver biopsy is not required to confirm the diagnosis in the ALF setting (the clinical picture and the biochemical markers are sufficient) and is hazardous given the coagulopathy; if needed it should be transvenous. [1]

Step 3 — Management of the ALF and its complications (5 marks): [1]

Cerebral oedema prophylaxis: elevate the head to 30 degrees, maintain normocapnia, normoglycaemia and normothermia, use hypertonic saline to a serum sodium of 145 to 155 mmol/L for grade 3 to 4 encephalopathy, and mannitol 0.5 g/kg for established intracranial hypertension. I would NOT use corticosteroids — they are ineffective for the cytotoxic cerebral oedema of ALF [8].

Coagulopathy: give vitamin K 10 mg IV to correct any reversible deficiency. Do NOT routinely correct the INR with fresh frozen plasma — the INR is the prognostic marker that drives the King's College Criteria and the transplant decision [6]. Reserve FFP, cryoprecipitate and platelets for active bleeding or immediately before procedures. The coagulopathy of ALF is a rebalanced state — the patient loses both procoagulant and anticoagulant factors, and is NOT auto-anticoagulated.

Haemolysis and transfusion: cross-match blood; transfuse for symptomatic anaemia or a haemoglobin below 70. [1]

Renal and haemodynamic support: use continuous renal replacement therapy (not intermittent, to avoid intracranial pressure surges) if renal failure develops; noradrenaline for vasodilatory shock. [1]

Infection surveillance: daily cultures; a low threshold for broad-spectrum antibiotics (sepsis precipitates encephalopathy and is frequently fatal). [1]

Step 4 — The transplant decision (2 marks): [1]

I would apply the King's College Criteria for non-paracetamol ALF continuously: INR above 6.5 alone, OR any three of age under 10 or over 40, non-A non-B or drug cause, jaundice to encephalopathy above 7 days, INR above 3.5, bilirubin above 300 [1]. However, for Wilson disease specifically, the cause itself is a poor prognostic factor — the near-universal medical mortality means transplant referral is mandatory regardless of whether the formal criteria are met. I would contact the transplant unit immediately, because the workup (blood group, imaging, psychosocial assessment, listing, donor matching) takes time. A patient who meets the criteria and does not receive a transplant has a survival of around 20 percent; with transplant, one-year survival exceeds 75 percent.

Step 5 — Chelation and adjunctive therapy (1 mark): [1]

I would start chelation (penicillamine or trientine) while awaiting transplant, acknowledging that it rarely reverses established ALF but is standard practice. NAC is continued empirically. [1]

Step 6 — Communication and genetic counselling (1 mark): [1]

I would speak with the patient (if rousable) and her family in plain language, explaining the diagnosis, the urgent need for transplant, and the prognosis honestly but without false hopelessness. I would involve the transplant coordinator, hepatology, surgery, anaesthesia and psychiatry. I would counsel the family that Wilson disease is autosomal recessive and that siblings have a 25 percent chance of being affected — they should be screened with caeruloplasmin, urinary copper and genetic testing. [1]

SAQ 2 — Paracetamol-induced acute liver failure: the King's College Criteria and the lactate adjunct (10 marks, 20 minutes)

Prompt: A 38-year-old man with chronic alcohol use presents 72 hours after a 25 g paracetamol overdose. He is in grade 3 encephalopathy. Bloods show AST 4500 U/L, INR 7.2, creatinine 320 micromol/L, arterial pH 7.25, arterial lactate 5.0 mmol/L, glucose 2.8 mmol/L. Paracetamol level 30 mg/L. Outline how you apply the King's College Criteria, the role of the lactate, and your integrated management plan. [1]

Model Answer

Step 1 — The King's College Criteria for paracetamol ALF (3 marks): [1]

For paracetamol-induced ALF, transplant referral is indicated if EITHER the arterial pH is below 7.3 after fluid resuscitation (alone sufficient), OR all three of INR above 6.5, creatinine above 300 micromol/L and grade 3 to 4 encephalopathy [1]. This patient meets the criteria on BOTH limbs — his arterial pH of 7.25 is below 7.3 (meeting the first limb alone), and he has the full triad (INR 7.2, creatinine 320, grade 3 encephalopathy). Either alone is sufficient. The single most common error in applying the paracetamol criteria is requiring all four components (pH plus the triad) — in fact, either the pH alone OR the triad alone is sufficient. I would refer him urgently to the liver transplant unit.

Step 2 — The lactate adjunct (2 marks): [1]

His arterial lactate of 5.0 mmol/L is above the 3.5 mmol/L early-admission threshold that Bernal showed identifies non-survivors with accuracy similar to the King's College Criteria combined, but a median of 6 hours earlier — 4 hours versus 10 hours [3]. The lactate is an early-warning adjunct that complements the criteria, not a replacement for them. Even if this patient had not yet formally met the KCC (for example, if the pH were 7.31 and the INR 5.5), the high lactate would trigger an early transplant conversation to buy time for workup and transfer.

Step 3 — The integrated management plan (3 marks): [1]

I would continue the 21-hour IV N-acetylcysteine regimen and extend it beyond 21 hours using the modified prolonged regimen, because Keays showed NAC improves survival even after fulminant hepatic failure is established [4]. I would manage the ALF in ICU: cerebral oedema prophylaxis (head elevation, hypertonic saline, mannitol for established intracranial hypertension, no corticosteroids), correct hypoglycaemia with 10 per cent dextrose and hourly monitoring, give vitamin K 10 mg without routine INR correction, support renal failure with continuous renal replacement therapy, and surveil for infection. I would start alcohol withdrawal prophylaxis (symptom-triggered benzodiazepines using CIWA-Ar, parenteral thiamine before glucose to prevent Wernicke, correct potassium, magnesium and phosphate). I would arrange the transplant workup urgently.

Step 4 — The coagulopathy trap and the communication (2 marks): [1]

I would NOT routinely correct the INR with FFP — the INR is the prognostic marker that drives the transplant decision [6]. I would give vitamin K 10 mg and reserve blood products for active bleeding or pre-procedure. I would communicate with the patient and family (with consent or under the doctrine of necessity if he lacks capacity from grade 3 encephalopathy) about the clinical course, the rationale for NAC and continued monitoring, and the urgent transplant referral. Once medically stable, I would involve the psychiatric liaison team for risk assessment and a safety plan.