Hepatic Encephalopathy

Reversible neuropsychiatric syndrome resulting from liver dysfunction and portosystemic shunting, allowing gut derived neurotoxins, principally ammonia, to bypass hepatic clearance and reach the brain, causing astrocyte swelling and altered neurotransmission.

Occurs in acute liver failure (see separate entry) and, more commonly in everyday practice, as a complication of decompensated cirrhosis.

Classified by the West Haven criteria: Grade I (subtle changes, mild confusion, altered sleep pattern, shortened attention span), Grade II (lethargy, disorientation, personality change, asterixis present), Grade III (marked confusion, somnolence but rousable, gross disorientation), and Grade IV (coma, unresponsive to stimuli).

Cognitive and personality change (often noticed first by family rather than the patient), altered sleep wake cycle (day night reversal), asterixis (flapping tremor on wrist extension, present from Grade II onward), fetor hepaticus, and, in advanced grades, progressive obtundation to coma.

Precipitants must always be actively sought: gastrointestinal bleeding (increased protein and blood load to the gut), infection (particularly spontaneous bacterial peritonitis), constipation, electrolyte disturbance (particularly hyponatremia and hypokalemia), dehydration or diuretic overuse, sedative or opioid use, and progression of underlying liver disease or a new portosystemic shunt (spontaneous or TIPS related).

Primarily clinical, based on the presence of known liver disease plus a compatible mental state change, ideally with a precipitant identified.

Ammonia level supports the diagnosis but correlates poorly with grade and is not required to make the diagnosis in a typical clinical picture.

Investigation is directed at finding the precipitant: FBC and CRP (infection), U&E (electrolytes, renal function), stool for occult blood or overt melena history, ascitic tap if ascites is present (neutrophil count above 250 cells per mm3 diagnostic of spontaneous bacterial peritonitis), and a careful medication review.

CT head is reserved for atypical presentations, focal neurological signs, or a history of trauma, to exclude intracranial hemorrhage, which cirrhotic patients are predisposed to given coagulopathy and thrombocytopenia.

Differentials include intracranial hemorrhage, other metabolic encephalopathies (uremia, hypoglycemia, hyponatremia), alcohol intoxication or withdrawal, Wernicke's encephalopathy, sepsis associated encephalopathy, and primary psychiatric illness.

• Identify and treat the precipitant, this is often the single most important intervention.

• Lactulose is first-line, titrated to achieve two to three soft stools per day; it works by acidifying the colon, trapping ammonia as ammonium and providing a laxative effect that reduces colonic transit time and bacterial ammonia production.

• Rifaximin is added for recurrent episodes despite adequate lactulose, reducing ammonia producing gut flora.

• Correct electrolyte disturbances, particularly hypokalemia and hyponatremia, both of which worsen encephalopathy independently.

• Nutritional support with adequate protein intake (protein restriction is no longer recommended, since it worsens muscle wasting and does not improve outcomes) should continue throughout.

• Airway protection is required in Grade III to IV encephalopathy given aspiration risk.

• Address underlying liver disease progression and consider whether the episode signals a need for transplant assessment in appropriate candidates.

Referral: hepatology for recurrent or refractory encephalopathy, or for transplant assessment if episodes reflect progressive decompensation.