Hepatic Encephalopathy — Viva

Q1: Definition and classification (2 min)

Define hepatic encephalopathy and classify it.

• HE = a reversible syndrome of impaired brain function occurring in patients with advanced liver disease and/or portosystemic shunting, in the absence of other identifiable neurological disease.

• Three classification axes:

  1. By underlying disease — Type A (acute liver failure, high cerebral oedema risk), Type B (portosystemic shunt without intrinsic liver disease), Type C (cirrhosis, commonest, over 80%).
  2. By severity (West Haven) — grade 0 covert/minimal (only psychometric testing), grade I trivial (sleep reversal, mild confusion), grade II lethargy and disorientation with asterixis, grade III somnolent but rousable with gross disorientation, grade IV coma. Grades II–IV are overt.
  3. By time course — episodic, recurrent (two or more in 6 months), persistent.

• High-yield: covert HE affects 30–60% of cirrhotics, impairs driving, predicts overt HE.

Q2: Pathophysiology (3 min)

Explain the pathophysiology of HE.

• Ammonia is central. Produced in the gut by urease-positive bacteria (Klebsiella, Proteus, E. coli) from dietary protein and from blood in GI bleeds; normally cleared by the liver via the urea cycle (mitochondrial) and periportal glutamine synthetase.
• In cirrhosis: reduced hepatocyte mass + portosystemic shunting → ammonia-rich portal blood reaches systemic circulation.
• Astrocyte cascade: ammonia crosses the BBB (as NH3 gas), taken up by astrocytes (the only brain cell with glutamine synthetase), converted to glutamine. Glutamine accumulation is osmotically active → astrocyte swelling (Alzheimer type II astrocyte — the histological hallmark).
• Swollen astrocyte cannot clear synaptic glutamate (loss of EAAT-2) → excitotoxicity; cannot maintain GABA/glutamate balance → increased GABA-ergic tone (somnolence, asterixis — and the reason benzodiazepines worsen HE).
• Synergistic toxin hypothesis: systemic inflammation (sepsis) sensitises brain to ammonia; manganese (T1 pallidal hyperintensity); mercaptans (fetor hepaticus); false neurotransmitters; zinc deficiency.
• Skeletal muscle is the major extra-hepatic ammonia disposal site (glutamine synthetase) — basis for high-protein diet to preserve muscle mass.

Q3: Management (3 min)

Outline the management of acute overt HE in a cirrhotic.

Four pillars, all in parallel:

1. Treat the precipitant. SBP (cefotaxime 2 g IV BD + IV albumin 1.5 g/kg day 1 then 1 g/kg day 3); GI bleed (terlipressin + antibiotics + endoscopy); constipation (lactulose/enema); correct electrolytes (slow Na correction — under 8 mmol/L per 24 h); stop sedatives; TIPS-related → shunt reduction.
2. Lower gut ammonia. Lactulose 15–30 mL every 1–2 hours titrated to 2–3 soft stools/day, then titrate down (endpoint is stool frequency, NOT ammonia level). Add rifaximin 550 mg BD for overt/recurrent HE — Bass 2010 NEJM showed 58% reduction in breakthrough HE when added to lactulose.
3. Secondary prophylaxis. Continue lactulose + rifaximin indefinitely; refer for liver transplant (1-year mortality 40–50% after first overt HE).
4. Supportive care. High protein 1.2–1.5 g/kg/day — do NOT restrict (Córdoba 2004 RCT); evening snack; thiamine in alcoholics; avoid benzodiazepines (use lorazepam/oxazepam if essential, propofol for ICU sedation); aspiration precautions.

Always check glucose first and give thiamine before any glucose in the alcoholic.

Q4: Complications and pitfalls (2 min)

List the complications and the classic pitfalls.

• Complications: aspiration pneumonia, falls and subdural in coagulopathic patients, pressure sores, DVT, cerebral oedema (especially Type A), recurrence (40% at 1 year), hepatic myelopathy, acquired hepatocerebral degeneration.
• Pitfalls: missing SBP as precipitant; restricting protein (causes sarcopenia); missing Wernicke; giving IV dextrose before thiamine; rapid Na correction (osmotic demyelination); using midazolam for ICU sedation; confusing HE with delirium tremens; missing a subdural; stopping rifaximin on discharge.