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Hepatology
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EMERGENCY

Hepatic Encephalopathy (HE)

High EvidenceUpdated: 2025-12-23

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Red Flags

  • GCS < 8 (Intubate for airway protection)
  • Signs of raised intracranial pressure (Cushing's triad)
  • Hypoglycaemia (common in liver failure)
  • Sepsis (SBP is a common precipitant)
Overview

Hepatic Encephalopathy (HE)

[!WARNING] Medical Disclaimer: This content is for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis and treatment. Medical guidelines and best practices change rapidly; users should verify information with current local protocols.

1. Overview

Hepatic Encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction and/or portosystemic shunting. It represents a reversible metabolic encephalopathy.

Key Concepts

  • Pathophysiology: Primarily driven by ammonia (and other gut-derived toxins) bypassing hepatic clearance and crossing the blood-brain barrier.
  • Classification:
    • Type A: Acute Liver Failure.
    • Type B: Bypass (Portosystemic shunts without cirrhosis).
    • Type C: Cirrhosis (Most common).
  • Precipitants: HE is almost always triggered by a precipitating event (infection, bleed, constipation) which must be identified and treated.

Clinical Scenario: The Confused Alcoholic

A 56-year-old male with known alcoholic cirrhosis is brought in by his partner because he is 'talking nonsense' and urinating in the hallway. On exam, he is drowsy but rousable. He has a coarse flapping tremor of the hands.

Key Teaching Points

  • The flapping tremor is **Asterixis**, the hallmark of Grade II HE.
  • Your priority is A (Airway) – is he safe? Then C (Circulation) – is he dry or bleeding?
  • Don't just give Lactulose! Find the trigger. Check for GI bleed (PR exam), Sepsis (CXR, Urine, Ascitic tap), and Constipation.
  • Ensure he is not hypoglycaemic.
2. Epidemiology
  • Prevalence: Overt HE occurs in 30–45% of patients with cirrhosis at some point.
  • Minimal HE (MHE): Up to 80% of cirrhotics may have subtle cognitive deficits (detectable only by psychometric testing) which affect driving ability and quality of life.
  • Mortality: 1-year survival after first episode of overt HE is ~40% without transplant.
3. Pathophysiology

The Ammonia Hypothesis

  1. Production: Ammonia (NH3) is produced in the gut by bacterial degradation of proteins and urea.
  2. Failure of Clearance: The failing liver cannot convert ammonia to urea (Ornithine cycle). Portosystemic shunts (varices/TIPS) allow ammonia to bypass the liver entirely.
  3. Brain Toxicity: Ammonia crosses the Blood-Brain Barrier (BBB).
  4. Astrocyte Swelling: Astrocytes convert ammonia + glutamate -> glutamine. Glutamine is osmotically active, drawing water into cells -> Cerebral Oedema (major cause of death in Acute Liver Failure, less so in chronic).
  5. Neurotransmission: Altered GABA-ergic and glutamatergic transmission.

Other Theories

  • False Neurotransmitters: Precursors (aromatic amino acids) increase, creating weak neurotransmitters (octopamine) that displace true ones.
  • GABA: Potentiation of GABA receptors (benzodiazepine-like effect).
4. Clinical Presentation

History (The Search for Precipitants)

Ask specifically about:

Physical Signs

Stool
Constipation? (Gut transit time increases ammonia absorption). Melaena? (GI bleed provides huge protein load).
Medication
New sedatives, opiates, diuretics?
Infection
Fever, dysuria, abdominal pain?
Diet
Excessively high protein meal (rarely a sole cause).
Volume
Diarrhoea/Vomiting (Dehydration -> alkalosis -> promotes NH3 entry to brain).
5. Clinical Examination
  1. Airway/GCS: Assess consciousness level. GCS < 8 needs intubation.
  2. Hydration: Dry mucous membranes? JVP?
  3. Abdomen:
    • Ascites? (Tap it to exclude SBP).
    • Tenderness?
    • Masses?
  4. Neurology: Elicit the flap. Test "Connection of Numbers" (Part A) on paper to screen for MHE.
6. Investigations

HE is a clinical diagnosis. Labs look for the cause.

Bloods

  • Ammonia: Controversial. Venous ammonia correlates poorly with grade of HE. High level supports diagnosis but normal level does not exclude it. Arterial ammonia is better but painful. Useful for monitoring in Acute Liver Failure, less so in chronic.
  • FBC/CRP: Screen for infection.
  • U&Es: Hypokalaemia (promotes renal ammonia production) and Hyponatraemia (worsens brain oedema). Dehydration (High Urea relative to Cr).
  • Glucose: Exclude hypo.
  • LFTs/INR: Assess synthetic function.

Imaging

  • CT Head: To exclude Subdural Haematoma (common in alcoholics due to falls + coagulopathy) or Intracranial Haemorrhage.
  • CXR: Pneumonia.

Procedures

  • Ascitic Tap: Essential in any cirrhotic with new confusion to rule out Spontaneous Bacterial Peritonitis (SBP).
7. Management

A. General Measures

  • Airway: Intubate if GCS < 8.
  • Nutrition: Do NOT restrict dietary protein. Malnutrition worsens outcomes. Patients need 1.2–1.5 g/kg/day of protein. (Only restrict transiently in severe, protein-intolerant cases).
  • Safety: Nurse in safe environment (falls risk).

B. Identify and Treat Precipitants

  1. Infection: Broad spectrum abx if SBP suspected.
  2. GI Bleed: Endoscopy/hemostasis.
  3. Constipation: Enemas.
  4. Dehydration: IV Fluids.
  5. Electrolytes: Correct Hypokalaemia aggressively.
  6. Drugs: Stop benzos/opiates/diuretics. Give Flumazenil if benzo overdose suspected.

C. Specific Therapy (Ammonia Lowering)

1. Lactulose (First Line)

  • Mechanism:
    • Cathartic (speeds up transit -> less absorption).
    • Acidifies gut lumen: Converts absorbable NH3 -> non-absorbable Ammonium (NH4+), which is trapped and excreted ("Ion Trapping").
    • Alters microbiome.
  • Dose: 30-45ml PO QDS initially, then titrate to aim for 2–3 soft stools per day.
  • Side Effects: Bloating, diarrhoea, dehydration (overuse).

2. Rifaximin (Second Line / Add-on)

  • Class: Non-absorbable antibiotic.
  • Mechanism: Reduces gut ammonia-producing bacteria.
  • Indication: Recurrent HE despite lactulose ("Frequent flyers"). Usually added to lactulose.
  • Efficacy: Reduces hospital admissions.

3. Other Agents

  • LOLA (L-ornithine L-aspartate): Substrate for urea cycle. Can lower ammonia but survival benefit unclear.
  • Branched-Chain Amino Acids (BCAA): May help.
8. Complications
  • Cerebral Oedema: High risk in Acute Liver Failure (Type A). Can lead to coning (herniation).
  • Aspiration Pneumonia: Due to low GCS.
  • Falls/Trauma.
9. Prognosis & Outcomes
  • Recurrent HE affects transplant candidacy and quality of life.
  • Persistence of HE despite treatment of precipitants is a poor prognostic sign (decompensated liver disease).
10. Evidence & Guidelines
  • EASL / AASLD Guidelines (2014): Recommendations on management of HE.
  • Rifaximin Trial (Bass et al., NEJM 2010): Rifaximin + Lactulose superior to Lactulose alone for maintaining remission.
11. Patient & Layperson Explanation

What is Hepatic Encephalopathy? It is confusion caused by liver failure. Normally, your liver cleans toxins (like ammonia) from your blood. When the liver is scarred (cirrhosis), it can't do this job, and blood also bypasses the liver through other veins. These toxins reach the brain and affect how it works.

What are the symptoms? It ranges from mild (being forgetful, mix-up day and night) to severe (very confused, sleepy, or even coma). A classic sign is a "flapping" tremor of the hands.

What triggers it? Usually something sets it off:

  • Constipation (waste stays in the gut longer).
  • Dehydration.
  • Infection.
  • Bleeding in the stomach.
  • Sleeping tablets.

How is it treated?

  1. Lactulose: A sweet syrup. It makes the gut more acidic (trapping toxins) and acts as a laxative to flush them out. The goal is 2-3 soft poos a day.
  2. Rifaximin: An antibiotic tablet that stays in the gut and reduces the bacteria that produce toxins.
  3. Treat the trigger: E.g., treating an infection or giving fluids.

Is it dangerous? Yes, severe confusion (coma) is a medical emergency. However, with treatment, most people wake up fully. It is a sign the liver is struggling, so regular review is needed.

12. References
  1. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.
  2. Bass NM, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081.
  3. Wong F. Management of hepatic encephalopathy in cirrhosis. Clin Liver Dis. 2020.

Last updated: 2025-12-23

At a Glance

EvidenceHigh
Last Updated2025-12-23
Emergency Protocol

Red Flags

  • GCS &lt; 8 (Intubate for airway protection)
  • Signs of raised intracranial pressure (Cushing's triad)
  • Hypoglycaemia (common in liver failure)
  • Sepsis (SBP is a common precipitant)

Clinical Pearls

  • glutamine. Glutamine is osmotically active, drawing water into cells -
  • Cerebral Oedema (major cause of death in Acute Liver Failure, less so in chronic).
  • promotes NH3 entry to brain).
  • non-absorbable Ammonium (NH4+), which is trapped and excreted ("Ion Trapping").

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines