Paediatrics chapters
Hepatic encephalopathy and acute liver failure in children
Brain dysfunction caused by liver failure: causes of acute liver failure in children, the stages of encephalopathy, the warning lab results, precipitating factors, intensive care management and when to list for transplant.
- Acute liver failure (fulminant hepatic failure) is severe liver injury with encephalopathy within 8 weeks of the first symptoms and no previous liver disease, with coagulopathy (PT over 15 seconds or INR over 1.5); causes include viral hepatitis (A, B, E), paracetamol and other drugs, Wilson disease, metabolic disease and autoimmune hepatitis.
- Hepatic encephalopathy ranges from subtle behaviour change (stage I) through confusion with asterixis (II), stupor (III) to coma (IV); it is caused by ammonia and other gut-derived toxins and is worsened by GI bleeding, infection, sedatives, hypokalaemia, constipation and high protein.
- Manage in ICU: airway, glucose (10% dextrose or more), treat coagulopathy with vitamin K and FFP when bleeding, lactulose, avoid sedatives, treat infection, control cerebral oedema (mannitol, fluid restriction) and refer early for liver transplantation.
On this page
Overview
Hepatic encephalopathy is a decline in brain function caused by liver failure. It may complicate acute liver failure (fulminant hepatic failure) or chronic liver disease (cirrhosis). In acute liver failure, encephalopathy is part of the definition and can progress from irritability to coma in hours. Survival depends on intensive supportive care and, for many children, liver transplantation.
Definitions
| Term | Definition |
|---|---|
| Acute (fulminant) liver failure | Serious liver injury in which encephalopathy appears within 8 weeks of the first symptoms, in a child without known chronic liver disease |
| Paediatric criteria (Akbar) | Biochemical acute liver injury (usually under 8 weeks), no chronic liver disease, and liver-based coagulopathy: PT over 15 seconds or INR over 1.5 |
| Hepatic encephalopathy | Deterioration of consciousness and brain function secondary to liver failure, acute or chronic |
In young children encephalopathy may be late or hard to detect; coagulopathy that does not correct with vitamin K is the key marker of liver failure.
Aetiology
Causes of acute liver failure
| Group | Causes |
|---|---|
| Infectious | Hepatitis A, B (with or without D), E, non-A to E hepatitis, herpes simplex (newborn), CMV, EBV, adenovirus, enteroviruses, parvovirus, sepsis |
| Drugs and toxins | Paracetamol (acetaminophen) overdose, valproate, isoniazid, phenytoin, carbamazepine, halothane, poisonous mushrooms (Amanita) |
| Metabolic | Wilson disease, galactosaemia, tyrosinaemia, hereditary fructose intolerance, fatty acid oxidation and mitochondrial defects, neonatal haemochromatosis |
| Autoimmune | Autoimmune hepatitis |
| Ischaemic / vascular | Shock, severe asphyxia, congestive heart failure, myocarditis, Budd-Chiari syndrome |
| Malignant | Acute leukaemia, lymphoproliferative disease |
Viral hepatitis is a leading cause of acute liver failure in children; think of Wilson disease in any child over 3 years with liver failure and Coombs-negative haemolysis.
Precipitants of encephalopathy (Akbar)
- Gastrointestinal bleeding (extra protein load in the gut)
- Infection / sepsis
- High-protein diet
- Constipation
- Sedatives (especially benzodiazepines) and opioids
- Hypokalaemia and alkalosis (diuretics, vomiting)
- Large paracentesis, dehydration
- Trauma or surgery
"Bleeding, Bugs, Bowels, Benzos, Burgers (protein), and low K".
Pathogenesis
- The failing liver cannot clear gut-derived toxins, and portosystemic shunting lets them bypass the liver.
- Main neurotoxins: ammonia (and glutamine), false neurotransmitters (octopamine), mercaptans, short-chain fatty acids, increased GABA activity and endogenous benzodiazepine-like compounds.
- Hypokalaemia causes alkalosis, which turns ammonium into ammonia that crosses the blood-brain barrier easily.
- Hypoglycaemia (failed glycogenolysis and gluconeogenesis) and hypoxia add to brain dysfunction.
- In acute failure, cerebral oedema and raised ICP develop; this is the leading cause of death.
Clinical features
General features of acute liver failure
- Fever, anorexia, vomiting, abdominal pain
- Deepening jaundice (absent in Reye syndrome)
- Bleeding: bruises, petechiae, nose and gum bleeding, GI bleeding
- Fetor hepaticus (sweet, musty breath)
- Ascites, oedema
- Liver may shrink rapidly: a falling liver span without clinical improvement is a bad sign
- Signs of chronic liver disease (spider naevi, splenomegaly) if acute-on-chronic
Stages of hepatic encephalopathy
| Stage | Clinical | Asterixis | EEG |
|---|---|---|---|
| I (prodrome) | Mild intellectual change, disturbed sleep-wake cycle, poor handwriting; infants irritable, fussy | Absent or slight tremor | Usually normal |
| II (impending coma) | Drowsy, confused, inappropriate behaviour, disorientation, mood swings, combative | Present | Generalised slowing |
| III (stupor) | Stuporous but rousable, incoherent speech, marked confusion, hyperreflexia | Present | Markedly abnormal, triphasic waves |
| IV (coma) | Unconscious; IVa responds to pain, IVb no response; later flaccid, areflexic | Absent | Slow delta waves, may become silent |
Asterixis disappears in deep coma (stage IV); its absence then is a bad sign, not an improvement.
Investigations
| Test | Typical finding |
|---|---|
| PT / INR | Prolonged; the most sensitive marker of synthetic failure; not corrected by vitamin K |
| Blood glucose | Hypoglycaemia, often hard to correct; check every 2 to 4 hours |
| Bilirubin | Marked conjugated hyperbilirubinaemia (often over 15 to 20 mg/dL) |
| ALT, AST | Very high (often over 1000 to 3000 U/L); a rapid fall with rising INR means massive necrosis, not recovery |
| Plasma ammonia | Raised (often 2 to 8 times normal) |
| Albumin | Low |
| Urea | Low (poor synthesis) or high (renal failure, GI bleed, dehydration) |
| Creatinine, urine output | Renal impairment, hepatorenal syndrome (low urine sodium) |
| Electrolytes | Hypokalaemia, hyponatraemia, low calcium, magnesium, phosphate |
| Blood gases | Respiratory alkalosis, later mixed metabolic acidosis, hypoxaemia |
| CBC and platelets | Thrombocytopenia; white count up (infection) or down (aplasia) |
| Blood, urine cultures | Sepsis (about half develop significant infection) |
| Cause-finding tests | IgM anti-HAV, HBsAg, IgM anti-HBc, anti-HEV, HSV PCR, paracetamol level, ceruloplasmin, urine copper, autoantibodies, metabolic screen (galactosaemia, tyrosinaemia) |
| Ultrasound with Doppler | Liver size and texture, ascites, hepatic and portal vein flow |
| EEG | Stage of encephalopathy |
| CT brain | Cerebral oedema, bleeding |
Differential diagnosis of altered consciousness
| Condition | Clue |
|---|---|
| Hypoglycaemia | Responds to glucose (check first in every drowsy child) |
| Meningitis / encephalitis | Fever, neck stiffness, CSF changes; liver tests near normal |
| Reye syndrome | After a viral illness (aspirin raises the risk); vomiting and encephalopathy with liver dysfunction but no deep jaundice |
| Urea cycle defects / organic acidaemias | Very high ammonia, normal or mildly abnormal liver tests, neonates or illness-triggered |
| Sepsis, shock | Hypotension, cold periphery, positive cultures |
| Drug or toxin ingestion | History, toxidrome |
| Intracranial haemorrhage | Coagulopathy, focal signs, CT |
| Diabetic ketoacidosis, uraemia, electrolyte disorders | Glucose, ketones, urea, sodium |
| Postictal state, cerebral malaria | History of seizures; malaria film |
Management
General measures
- Manage in ICU, ideally at a centre that offers liver transplantation.
- ABC: oxygen; intubation and ventilation for stage III to IV coma.
- IV access, nasogastric tube, urinary catheter, strict fluid balance; hourly vital signs.
- Treat the cause where possible:
| Cause | Specific treatment |
|---|---|
| Paracetamol poisoning | N-acetylcysteine |
| Herpes simplex | Aciclovir |
| Hepatitis B | Lamivudine (antiviral) |
| Autoimmune hepatitis | Prednisolone |
| Galactosaemia | Remove galactose from diet |
| Wilson disease | Chelation and urgent transplant assessment |
Specific supportive measures
| Problem | Management |
|---|---|
| Hypoglycaemia | IV glucose with 10% dextrose or stronger; frequent bedside checks |
| Coagulopathy | IV vitamin K; FFP, cryoprecipitate and platelets for active bleeding or procedures (Nelson); Akbar also corrects very marked prolongation (PT over 40 seconds) to prevent intracranial bleeding. Blood products make the INR harder to interpret |
| GI bleeding prevention | IV H2 blocker or PPI; sucralfate |
| Encephalopathy | Lactulose by NG tube, adjusted to give several soft stools a day; rifaximin or neomycin to reduce ammonia-forming bacteria; enemas if constipated; limit protein (Akbar: 0.5 to 1 g/kg/day) while keeping calories up |
| Sedation | Avoid sedatives; benzodiazepines are contraindicated; if essential for agitation, use the least harmful option under specialist advice |
| Cerebral oedema | Fluid restriction (Akbar: under 75% of maintenance), IV mannitol, short-term hyperventilation; avoid hyponatraemia |
| Infection | High suspicion; broad-spectrum antibiotics (avoid aminoglycosides, which harm the kidney); antifungals if needed |
| Ascites | Restrict fluid and sodium, albumin infusion |
| Renal failure | Keep circulating volume, albumin if low, diuretics if overloaded, dialysis or haemofiltration |
| Electrolytes | Correct potassium, sodium, calcium, magnesium, phosphate |
Lactulose is broken down by colonic bacteria into acids. The acidic colon traps ammonia as ammonium, and the laxative effect clears nitrogenous material.
Liver transplantation
- The only definitive treatment when the liver does not recover.
- Akbar: indicated for children reaching stage III or IV coma (mortality over 70% without transplant) and in all forms of fulminant failure (viral, paracetamol, Wilson).
- Irreversible brain damage is a major contraindication.
Complications
- Cerebral oedema and brain herniation (commonest cause of death)
- Bleeding: GI, intracranial, pulmonary
- Sepsis (bacterial and fungal)
- Hepatorenal syndrome: oliguria, rising creatinine, low urine sodium
- Hypoglycaemia, electrolyte and acid-base disorders
- Respiratory failure, aplastic anaemia (after non-A to G hepatitis)
Prognosis
- Depends on cause and depth of coma.
- Fulminant hepatitis A has the best overall survival (about 68% in Akbar); other causes do worse.
- Poor prognostic signs (Akbar): jaundice for more than 7 days before encephalopathy, PT over 50 seconds, bilirubin over 17.5 mg/dL, stage IV coma, age under 10 years, a shrinking liver and refractory hypoglycaemia.
Expect: the definition (encephalopathy within 8 weeks, no chronic liver disease; INR over 1.5 or PT over 15 s); common causes (viral hepatitis, paracetamol, valproate, Wilson disease, metabolic disease); stages I to IV with asterixis in stage II to III and its loss in coma; precipitants (GI bleed, infection, sedatives, hypokalaemia, constipation, protein); ammonia and GABA in pathogenesis; hypoglycaemia as the commonest metabolic emergency; lactulose, rifaximin or neomycin; benzodiazepines contraindicated; cerebral oedema as the commonest cause of death; and transplant for stage III to IV coma.
Quick revision
- Acute liver failure: encephalopathy within 8 weeks, no chronic disease, INR over 1.5.
- Causes: hepatitis A, B, E; paracetamol, valproate, isoniazid; Wilson; galactosaemia; autoimmune.
- Stage I sleep and behaviour change; II confusion, asterixis; III stupor; IV coma.
- Precipitants: GI bleed, sepsis, sedatives, hypokalaemia, constipation, high protein.
- Tests: INR, glucose, ammonia, bilirubin, electrolytes, cultures, cause screen.
- ICU, glucose, vitamin K, FFP if bleeding, lactulose, no benzodiazepines, antibiotics.
- Cerebral oedema = commonest cause of death; mannitol and fluid restriction.
- Transplant for stage III to IV; poor signs: PT over 50 s, bilirubin over 17.5 mg/dL.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
What is the earliest sign of hepatic encephalopathy in an infant?
Subtle irritability, fussiness and poor feeding, often with a disturbed sleep pattern; drowsiness and confusion follow.
Why is a falling ALT not always good news?
In acute liver failure a falling ALT with a rising INR, deepening jaundice and a shrinking liver means few hepatocytes are left, which is a sign of worsening failure.
Why are benzodiazepines avoided?
They act on the same GABA system that is overactive in hepatic encephalopathy and can deepen coma.
When should a child be referred for liver transplant?
As soon as acute liver failure is recognised, and urgently once encephalopathy reaches stage III or IV or poor prognostic signs appear.