Write a short note on hepatic encephalopathy.

Definition

Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome occurring in patients with liver dysfunction or portosystemic shunting, after exclusion of other causes of brain dysfunction. It ranges from subtle cognitive changes detectable only on testing to deep coma.

Classification (by underlying condition): Type A — with Acute liver failure; Type B — with portosystemic Bypass without intrinsic liver disease; Type C — with Cirrhosis (the commonest).

Pathogenesis

• Ammonia is the central mediator. Gut bacteria and enterocytes produce ammonia from nitrogenous substrates; the failing liver cannot convert it to urea, and portosystemic shunting allows it to bypass the liver and reach the systemic circulation.
• Ammonia crosses the blood–brain barrier and is metabolised by astrocytes, converting glutamate to glutamine. Accumulated glutamine acts as an osmolyte, causing astrocyte swelling — producing cerebral oedema in acute liver failure and low-grade oedema with Alzheimer type II astrocytosis in cirrhosis.
• Contributing factors: inflammation and cytokines, increased GABAergic tone with endogenous benzodiazepine-like substances, oxidative stress, manganese deposition in the basal ganglia, and altered gut microbiota.

Important caveat: serum ammonia correlates poorly with the grade of encephalopathy, and a normal ammonia does not exclude HE. It is a clinical diagnosis — measuring ammonia repeatedly to "monitor" HE is a common error.

PRECIPITATING FACTORS — the practical core of management

Clinical Features and Grading — West Haven Criteria

Signs:

• asterixis (flapping tremor) — a coarse, irregular, negative myoclonus best elicited with the arms outstretched and wrists dorsiflexed (absent in coma, and not specific — it also occurs in uraemia, CO2 retention and drug toxicity)
• fetor hepaticus (a sweet, musty breath odour)
• hyperreflexia and extensor plantars
• constructional apraxia (inability to draw a five-pointed star).

Investigations are directed at finding the precipitant and excluding alternatives: CBC, ascitic tap for SBP, cultures, electrolytes, renal function, glucose, arterial ammonia (of limited value), and CT head to exclude subdural haematoma — an important consideration in a coagulopathic patient who may have fallen.

Management

1. Identify and treat the precipitant — this is the most important step and resolves most episodes

Treat infection (always tap the ascites), control gastrointestinal bleeding, correct electrolytes and dehydration, relieve constipation, and stop sedatives and diuretics.

2. Reduce ammonia production and absorption

• Lactulose — first-line. A non-absorbable disaccharide fermented by colonic bacteria to short-chain fatty acids, which acidify the colon, converting absorbable ammonia (NH3) to non-absorbable ammonium (NH4+), and which act as a cathartic. Titrate the dose to 2–3 soft stools per day — under-dosing and over-dosing (causing dehydration and hypokalaemia, which worsen HE) are both common errors. Give by nasogastric tube or enema in the comatose patient.
• Rifaximin — a poorly absorbed antibiotic that reduces ammonia-producing gut flora; added to lactulose it reduces recurrence and hospitalisation, and is the standard for secondary prophylaxis.
• L-ornithine L-aspartate (LOLA) — enhances ammonia detoxification; used as an adjunct.
• Older agents: neomycin and metronidazole (limited by toxicity).

3. Nutrition — an area of frequent, harmful error

Do NOT restrict protein. Patients with cirrhosis are catabolic and sarcopenic, and protein restriction worsens muscle loss — and since muscle is an important site of ammonia disposal, restriction ultimately worsens encephalopathy. Give adequate protein (1.2–1.5 g/kg/day), preferring vegetable and dairy protein, in small frequent meals with a late-evening snack.

4. Supportive care

Airway protection and intubation in grade III–IV; nursing care; avoid sedation (if unavoidable, use short-acting agents); treat coagulopathy only if bleeding; and manage cerebral oedema in acute liver failure.

5. Long-term

• Secondary prophylaxis with lactulose plus rifaximin after an episode
• treat the underlying liver disease
• avoid sedatives and alcohol
• counsel about driving, since even covert encephalopathy impairs driving ability
• refer for liver transplant assessment — an episode of overt encephalopathy is a marker of decompensation and poor prognosis.