Level 2 of 6Must-remember

Acute liver failure

Assess, manage and stay safe — enough on its own

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The card — assess, manage, caution

Assessment— look, ask, measure

Make the diagnosis on the triad: acute liver failure is the rapid deterioration of liver function in a patient without pre-existing liver disease, defined by acute liver injury, coagulopathy with an INR of 1.5 or higher, and hepatic encephalopathy of any grade — all three elements are required.Not available at your setup — Coagulation (PT/INR).
Jaundice and coagulopathy without encephalopathy is severe acute liver injury, a precursor state with the same causes and demanding the same vigilance — the appearance of encephalopathy is the cardinal event.
Take the drug history obsessively: paracetamol (dose, timing, staggered ingestion over many hours, several proprietary preparations taken together — all frequently denied because the patient does not consider them an overdose), antibiotics, antituberculosis drugs, antiepileptics, and herbal and dietary supplements, which patients omit because they do not classify them as medicines.
Ask what lowered the toxic threshold: chronic alcohol use, fasting or malnutrition, weight-loss surgery, or enzyme-inducing drugs.
Expect an unremarkable prodrome: nausea, vomiting, anorexia, malaise, weakness and right upper quadrant discomfort, often attributed to a viral illness.
Cerebral disturbance is the cardinal manifestation — reduced alertness, poor concentration, slowed mentation, a disordered sleep rhythm, irritability and personality change, progressing through restlessness and aggressive outbursts (and in ALF specifically excitability and mania) to drowsiness, delirium, stupor and coma.
Grade the encephalopathy and write the time beside it: grade 1 poor concentration, slurred speech, slow mentation, disordered sleep; grade 2 drowsy but easily rousable, occasional aggression, lethargic, flapping tremor; grade 3 marked delirium, responds to pain and voice, gross disorientation, flapping tremor; grade 4 unresponsive to voice, may or may not respond to pain, unconscious. A single grade is nearly worthless; serial timed grades are the disease's own trend line.
Use the bedside instruments: asterixis (flapping tremor of the outstretched, dorsiflexed hands, and of the body and tongue), constructional apraxia (inability to copy a five-pointed star or draw a clock face), the trail-making test (normal 15–30 seconds), and fetor hepaticus, a slightly sweet ammoniacal odour.
Do not rely on jaundice: it may be absent or minimal at the outset, particularly in paracetamol overdose, is rare in Reye syndrome, and death may occur in hyperacute liver failure before jaundice develops.
Read the abdomen for what is absent: the liver is usually of normal size and becomes smaller as disease advances; hepatomegaly is unusual and hepatomegaly with sudden-onset ascites suggests Budd–Chiari syndrome; splenomegaly is uncommon and never prominent — a large spleen indicates that the liver disease is chronic, as do spider telangiectasia, palmar erythema, leuconychia, gynaecomastia, testicular atrophy, Dupuytren's contracture and caput medusae.
Check a capillary blood glucose immediately and at least 2-hourly in the acute phase — hypoglycaemia is common, often profound, is the commonest reversible cause of drowsiness in a child, and causes permanent injury if missed.
Hunt actively for signs of rising intracranial pressure: unequal or abnormally reacting pupils, fixed pupils, hypertensive episodes, bradycardia, hyperventilation, profuse sweating, local or generalised myoclonus, focal fits and decerebrate posturing — papilloedema occurs rarely and is a late sign, so its absence excludes nothing.
Hepatic encephalopathy rarely causes focal neurological signs; if these are present, other causes must be sought — a hemiparesis, a unilateral fixed pupil or a new cranial nerve palsy in a jaundiced, confused patient mandates cross-sectional imaging of the brain, not more lactulose, and subdural haematoma in a coagulopathic patient who has fallen is the classic trap.Not available at your setup — CT scan.
Record the other red flags: progressive prolongation of the prothrombin time (the point at which high-dependency or intensive care becomes necessary), arterial pH below 7.3, arterial lactate above 3.5 mmol/L, oliguria or a rising creatinine, and any unexplained deterioration — which in this disease means infection until proved otherwise.Not available at your setup — Coagulation (PT/INR), Arterial blood gas, Renal function (creatinine/urea).
Send a paracetamol level and toxicology screen in every case, whatever the history — but know that paracetamol is undetectable in plasma in 50% of cases, particularly in patients who present already in liver failure, so a negative level does not exclude it as the cause.
Know the population shifts: age over 40 years and age under 10 years are each adverse prognostic criteria; children decompensate faster because glycogen stores are small and metabolic rate high, and in a small child irritability, inconsolable crying, a reversed sleep pattern, refusal to feed and unusual sleepiness are the paediatric equivalents of grades 1–2; in pregnancy fear acute fatty liver of pregnancy and hepatitis E, in which aminotransferases may be only modestly raised (under 300 U/L).

Management— do this, in order

Move the patient early: monitor closely and treat in a high-dependency or intensive care environment as soon as progressive prolongation of the PT occurs or hepatic encephalopathy is identified, not once they become unstable.Not available at your setup — ICU / HDU bed. high-dependency environment if full intensive care is unavailable
Airway: grade 3 or 4 encephalopathy means the airway is not safe — intubate for airway protection, and also for inability to clear secretions or hypoxaemia despite high-flow oxygen. Nurse the patient head-up at 30 degrees with the neck straight, the position that reduces both intracranial pressure and aspiration risk.Doctor / NurseNot available at your setup — Endotracheal intubation kit.
Circulation: preserve intravascular volume with isotonic crystalloid in repeated boluses with reassessment, and avoid large-volume infusions of hypotonic fluids, which worsen cerebral oedema — never 5% dextrose or 0.45% saline as a resuscitation or maintenance fluid in an encephalopathic patient; where dextrose is needed for hypoglycaemia give it as a concentrated solution through a dedicated line.
If hypotension persists after adequate volume, noradrenaline is the preferred vasopressor; vasopressin may be added for persistent hypotension.Doctor / NurseNot available at your setup — Infusion pump.
Prevent hypoglycaemia rather than merely treating it: measure capillary glucose immediately and at least 2-hourly in the acute phase, and run a continuous glucose-containing infusion.
Give N-acetylcysteine early to all patients in whom paracetamol toxicity is suspected — do not wait for a level. Intravenous adult and paediatric mg/kg doses are the same: 150 mg/kg in 200 mL 5% dextrose over 60 minutes, then 50 mg/kg in 500 mL 5% dextrose over 4 hours, then 100 mg/kg in 1000 mL 5% dextrose over 16 hours.Doctor / NurseNot available at your setup — Infusion pump.
In children the diluent volume must be reduced to avoid iatrogenic hyponatraemia, which worsens cerebral oedema — for a child under 20 kg, approximately 3 mL/kg, 7 mL/kg and 14 mL/kg of 5% dextrose for the three infusions respectively; the oral regimen (adult and paediatric) is 140 mg/kg orally, then 70 mg/kg every 4 hours for a further 17 doses, only in a fully alert patient who is not vomiting.
Anaphylactoid reactions to N-acetylcysteine are rate-related, not true allergy: stop the infusion, give an antihistamine, and restart at a slower rate.Doctor / Nurse
Treat the cause where a treatment exists: stop the culprit drug and every other non-essential drug in idiosyncratic DILI and record the stop date; give intravenous aciclovir 10 mg/kg every 8 hours (adult and paediatric) empirically if herpes simplex hepatitis is suspected, because it is treatable and lethal if missed; a nucleos(t)ide analogue (entecavir or tenofovir) for acute hepatitis B; delivery for acute fatty liver of pregnancy and HELLP; restore cardiac output in ischaemic hepatitis.Doctor / Nurse
Give vitamin K, and only vitamin K, for the coagulopathy: phytomenadione 10 mg by slow intravenous injection once daily for up to 3 days in adults, 250–300 micrograms/kg (maximum 10 mg) once daily in children — blood products are indicated only for active major haemorrhage, or immediately before an unavoidable invasive procedure.Doctor / NurseNot available at your setup — Blood & blood products.
Minimise rises in intracranial pressure by general measures first: head elevated to 30 degrees with the neck midline; minimal handling and clustering of interventions; a quiet, dimly lit environment; treatment of fever, pain, hypoglycaemia and seizures; avoidance of hypotonic fluids; and adequate sedation once the airway is secured.
Osmotherapy for signs of intracranial hypertension: mannitol 20%, 0.5–1 g/kg intravenously over 15–20 minutes, adult and paediatric dose the same; or hypertonic saline, commonly used to maintain a serum sodium of about 145–155 mmol/L. Mannitol requires renal excretion and must be used with great caution in the oliguric patient unless renal replacement therapy is available; short-term hyperventilation is a temporising measure only.Doctor / Nurse
Bowel-directed treatment for encephalopathy — never orally to a patient with an unprotected airway: lactulose 30–60 mL orally every 2 hours until improved mental status or a first bowel movement, then titrate to 2–3 bowel movements per day; paediatric starting doses 1 month to 1 year 2.5 mL twice daily, 1–5 years 5 mL twice daily, 5–18 years 10 mL twice daily, titrated to 2–3 soft stools daily; a phosphate or lactulose enema where the oral route is compromised; rifaximin 550 mg orally twice daily.
Seek and reverse every precipitant item by item: drugs (especially sedatives and antidepressants); dehydration including from diuretics and large-volume paracentesis; portosystemic shunting including a previous TIPS; infection; acute kidney injury; hypokalaemia; hyponatraemia; constipation; and an increased protein load including gastrointestinal bleeding.
Screen for infection on admission and repeat with any deterioration: blood, urine, throat, sputum and cannula site cultures, a chest radiograph and temperature charting — for suspected sepsis, broad coverage is indicated and should not await confirmation.Doctor / NurseNot available at your setup — Blood culture.
Suspect and treat spontaneous bacterial peritonitis in any patient with ascites — abdominal signs are mild or absent in about a third and it may present with encephalopathy alone; an ascitic neutrophil count above 250 × 10⁶/L almost invariably indicates infection. Treat with cefotaxime 2 g intravenously every 8 hours (paediatric 50 mg/kg every 8 hours) or piperacillin/tazobactam, and give intravenous albumin 1.5 g/kg on day 1 and 1.0 g/kg on day 3 to patients with jaundice or renal impairment.Doctor / Nurse
Feed the patient and protect the stomach: do not restrict protein — maintain no less than 60–80 g/day in the presence of encephalopathy, with enteral protein at 1–1.5 g/kg/day if oral intake cannot resume within 5–7 days; give stress gastropathy prophylaxis with pantoprazole 40 mg intravenously daily in an adult, 0.5–1 mg/kg (maximum 40 mg) daily in a child.
Refer for transplant assessment on trajectory, not on threshold — a rising INR, a rising bilirubin, a rising creatinine or a deepening encephalopathy grade — because liver transplantation is the only definitive treatment for irreversible acute liver failure and one-year survival after transplantation for ALF is 80–90%.

Caution— what harms

Coagulopathy should generally not be corrected. Fresh frozen plasma blinds the prothrombin time — the most valuable prognostic test and the basis of the transplant criteria — and the coagulopathy is a rebalanced state in which clinically significant bleeding is uncommon and reflects severe systemic inflammation rather than the coagulopathy itself.Not available at your setup — Coagulation (PT/INR).
Do not sedate. Sedatives are a listed precipitant of hepatic encephalopathy and are cleared poorly by the failing liver — a benzodiazepine given to settle a restless grade 2 patient can produce a grade 4 patient who then requires intubation; treat restlessness by finding its cause (hypoglycaemia, hypoxia, pain, a full bladder, developing intracranial hypertension), and where agitation genuinely threatens the airway the answer is definitive airway control with appropriate sedation, not sedation without airway control.Doctor / Nurse
Flumazenil is not a treatment for hepatic encephalopathy — it has a place only in confirmed benzodiazepine poisoning, and may provoke seizures in mixed overdose or dependence.Doctor / Nurse
Never give large volumes of hypotonic fluid, and never use 5% dextrose or 0.45% saline as resuscitation or maintenance fluid in an encephalopathic patient — they worsen cerebral oedema.
Falling aminotransferases are not recovery: in paracetamol toxicity they are towering (above 5000 U/L, 100–500 times normal) but fall as liver damage progresses — a falling ALT with a rising INR and bilirubin means the patient is deteriorating.Not available at your setup — Liver function tests, Coagulation (PT/INR).
A normal albumin is a false comfort, because albumin has a half-life of around 20 days and remains normal unless the course is prolonged; a low albumin points instead towards chronic liver disease.Not available at your setup — Liver function tests.
A negative paracetamol level excludes nothing — the drug is undetectable in plasma in 50% of cases, particularly in patients who present already in liver failure.
Never delay treatment for an ammonia result: ammonia is prognostic, not diagnostic — increased concentrations occur in the absence of clinical encephalopathy — although intracranial hypertension rarely develops below 75 micromol/L and is more likely above 200 micromol/L.
Do not restrict dietary protein: it worsens the nutritional state of an already malnourished patient, and protein should be maintained at no less than 60–80 g/day.
Do not overshoot with lactulose: diarrhoea, dehydration and hypokalaemia precipitate more encephalopathy.
Corticosteroids do not reduce mortality in acute liver failure and may lower overall survival in patients with a high MELD score, despite the high rate of adrenal insufficiency; routine prophylactic antibiotics reduce infection but not mortality and are not routinely recommended; and percutaneous liver biopsy is contraindicated because of the severe coagulopathy (use the transjugular route where histology will change management).
A normal CT head does not mean the brain is safe — CT is not a reliable early test for cerebral oedema; use it for focal signs, seizures, a fall, anticoagulation or unexplained failure to improve, principally to exclude intracranial haemorrhage.Not available at your setup — CT scan.
Infection complicates up to 90% of cases and frequently occurs without fever or leucocytosis, with a deepening encephalopathy as the only sign — absence of leucocytosis does not exclude infection, and fungal infection, particularly candidaemia, is characteristic of the second week.Not available at your setup — Blood culture.
The Child–Pugh and MELD scores do not apply to acute liver failure; they belong to the patient whose diagnosis is actually cirrhosis or acute-on-chronic liver failure — and the adverse prognostic criteria are a warning, not a starting gun, since assessment on threshold is late by definition.

Refer / escalate

Refer to a transplant centre and to intensive care early — as soon as the prothrombin time is progressively prolonging or any grade of encephalopathy appears, and always **before** the adverse prognostic criteria are met, because meeting either King's College set implies a mortality of 90% or more without transplantation while one-year survival after transplantation is 80–90%; escalate immediately for grade 3 or 4 encephalopathy (the airway is not safe), signs of rising intracranial pressure, focal neurological signs, arterial pH below 7.25–7.3, lactate above 3.5 mmol/L, creatinine above 300 micromol/L or anuria, or any unexplained deterioration.

The card — assess, manage, caution

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