Gastroenterology & Nutrition

Acute Liver Failure

Massive hepatocyte necrosis in a liver with no pre-existing disease strips out clotting-factor synthesis and ammonia clearance, so coagulopathy and encephalopathy appear together within days to weeks.

In a nutshell

Acute liver failure is coagulopathy of liver origin with hepatic encephalopathy of any grade, in a person with no pre-existing liver disease. Paracetamol causes most UK cases: give intravenous acetylcysteine 100 mg/kg over 2 hours then 200 mg/kg over 10 hours, and telephone a liver unit.

Classic presentation

A previously well young adult, two days after a paracetamol overdose, is jaundiced and confused with a rising INR, hypoglycaemia and a metabolic acidosis.

Key points

Adult under 40 kg: the same 100 then 200 mg/kg of acetylcysteine, given as a 50 mg/mL solution over 2 hours then a 10 mg/mL solution over 10 hours.
Hyperacute failure carries the highest risk of cerebral oedema yet the best chance of recovery without transplantation. Subacute failure is the reverse.
Vitamin K will not fix a liver coagulopathy, but it removes dietary deficiency as a confounder. Give phytomenadione very slowly intravenously: anaphylactoid reactions have been reported.
The King's College criteria are 82 to 95% specific but only 58 to 69% sensitive for death, so a patient can die without ever meeting them.
Start renal replacement for potassium above 6 mmol/L, bicarbonate below 15 mmol/L or creatinine above 400 micromol/L.
Avoid arterial puncture except after paracetamol overdose, where the lactate is prognostic. Avoid NSAIDs and intramuscular injections in everyone.
Extracorporeal whole liver perfusion should be used only in research: NICE found the evidence on efficacy inadequate in quantity and quality.
Survival has improved steadily over recent decades, from approximately 20% to greater than 60%, through better critical care and emergency liver transplantation.

First-line investigation

INR and coagulation screen, capillary glucose, arterial gas for pH and lactate, U&E, liver tests and a plasma paracetamol concentration, all sent on arrival.

Management

Resuscitate, stop hepatotoxins, grade the brain

ABCDE, oxygen, capillary glucose and two cannulae. Support circulating volume with balanced crystalloid or sodium chloride 0.9%, withdraw hepatotoxic medicines and involve intensive care for any encephalopathy.^3,1
Grade 1: behaviour change, minimal change in consciousness. Grade 2: drowsy, grossly disorientated, possibly asterixis. Grade 3: marked confusion, incoherent, rouses to voice. Grade 4: comatose, decerebrate or decorticate posturing.^2,1
Do not sedate: sedation hides the grade. Repeat the grading often, because deterioration can be precipitous once encephalopathy has started.^3,1

Telephone the liver unit at these numbers

Call at an INR above 2 or prothrombin time above 20 seconds, pH below 7.3, creatinine above 200 micromol/L, hypoglycaemia, or any impaired consciousness.³
There are seven UK liver transplant centres. King's takes referrals via its online liver urgent referral system, then a call to the on-call liver registrar through switchboard.^5,6,1
Level 2 or 3 bed, or high-grade encephalopathy: ask for the Liver Intensive Therapy Unit team. Most paracetamol cases go straight there.⁶

Acetylcysteine: the SNAP (Scottish and Newcastle Acetylcysteine Protocol) 12-hour regimen

Treat whenever paracetamol cannot be excluded, including beyond 48 hours. If the timing is in doubt or the ingestion spanned over an hour, treat without a nomogram.^4,2
Adult 40 kg or more: 100 mg/kg in 200 mL glucose 5% intravenously over 2 hours, then 200 mg/kg in 1 litre over 10 hours.⁷
Total 300 mg/kg over 12 hours, calculating weight capped at 110 kg. Use sodium chloride 0.9% if glucose 5% is unsuitable.⁷
SNAP is default in all emergency departments per the Royal College of Emergency Medicine. Licensed alternative: 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours.^8,7

Glucose, clotting and the other organs

Glucose below 4 mmol/L: give 15 to 20 g intravenously over 15 minutes as glucose 10% or 20%, then run glucose 10% at 100 mL/hour. Check glucose every 2 hours and urine output each hour.^9,10,3
Run sodium chloride 0.9% alongside the glucose to avoid hyponatraemia. Add potassium chloride 40 mmol/L if hypokalaemic, never exceeding 10 mmol/hour.³
A GGC specialist pathway uses phytomenadione 10 mg by slow IV injection over 3 to 5 minutes on days 1, 2 and 3. Confirm the local liver-unit regimen; no fresh frozen plasma unless bleeding.^3,1,11
Culture blood and urine at baseline and every 24 hours. Renal replacement at potassium above 6 mmol/L, bicarbonate below 15 mmol/L or creatinine above 400 micromol/L.³

Encephalopathy, airway and intracranial pressure

At grade 2, transfer to a specialist centre, elevate the head 20 to 30 degrees and avoid stimulation. Lactulose 30 to 50 mL three times daily may achieve two or three soft stools.^2,3,12
Intubate and sedate at grade 3 or 4 encephalopathy, and sooner if the patient cannot protect the airway or is failing to oxygenate or ventilate.²
Mannitol 20% 0.5 g/kg intravenously over 30 to 60 minutes, for imminent herniation or severe raised intracranial pressure only, and never outside critical care.^3,2,13

Transplant criteria, and what they miss

Paracetamol arm: arterial pH below 7.3 after fluid resuscitation. That alone qualifies a patient for super-urgent listing.^2,1
Or all three co-existing: INR above 6.5 (prothrombin time above 100 seconds), creatinine above 300 micromol/L, and grade 3 to 4 encephalopathy.^2,5,1
Non-paracetamol arm: INR above 6.5 alone. Or any three of: age under 10 or over 40, non-A/non-B or drug-induced cause, jaundice to encephalopathy over 7 days, INR above 3.5, bilirubin above 300 micromol/L.^5,1
NHS Blood and Transplant's current listing policy uses pH below 7.25 beyond 24 hours, and lactate above 5 mmol/L on admission with above 4 mmol/L at 24 hours.⁵

Cause-specific treatment, and what only the centre does

Stop the suspect drug. Aciclovir for suspected herpes simplex or varicella zoster, immunosuppression for autoimmune hepatitis, delivery for pregnancy-related failure, listing for Wilson disease and Budd-Chiari syndrome.^2,1
In confirmed non-paracetamol failure, acetylcysteine's effect on mortality and transplant rate is inconclusive, so it is a liver-unit decision. Use extracorporeal whole liver perfusion only in research.^14,15

Exam traps

A very high ALT alone is acute liver injury. Without encephalopathy it is not liver failure, and a rising ALT is not a reason to phone the transplant unit.
Do not correct the INR with fresh frozen plasma to make the number look better. It is the prognostic monitor the transplant unit needs to see.
Do not sedate a patient you have not yet graded: sedation hides the encephalopathy grade that decides transfer, intubation and listing.
Exam questions quote the original King's threshold of arterial pH below 7.3. NHS Blood and Transplant's current listing policy uses pH below 7.25 beyond 24 hours.
Clubbing, spider naevi, ascites, splenomegaly or a large liver point to decompensated cirrhosis, a different disease with a different prognosis and pathway.
In confirmed non-paracetamol failure the evidence that acetylcysteine improves mortality or transplant rate is inconclusive, unlike its established role in paracetamol poisoning.
This encephalopathy swells the brain. Unlike in cirrhosis, it can progress to raised intracranial pressure and herniation within hours of starting.

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.