Hepatic Encephalopathy

Count stools, episodes, and TIPS timing, not ammonia targets

The 2026 ACG anchors tie treatment to bowel safety, recurrence, elective TIPS prevention, and transplant access.

After initial catharsis and mental-status improvement, titrate maintenance lactulose to approximately 2 to 3 soft bowel movements per day.

After overt HE, lactulose is first-line outpatient prophylaxis; add rifaximin for breakthrough or recurrent overt HE despite an adequate lactulose plan.

For elective TIPS, start rifaximin 14 days before the procedure and continue for at least 6 months; refractory post-TIPS HE requires shunt-focused review, and multiple episodes with MELD below 15 can justify living-donor transplant evaluation.

The spectrum runs from covert dysfunction to coma

Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting, with fluctuating manifestations.

Covert HE includes subtle or psychometrically detected deficits that can impair driving, work, sleep, and quality of life without obvious disorientation.

Overt HE ranges from altered attention and sleep-wake behavior through disorientation, somnolence, and coma.

Asterixis is negative myoclonus that supports a toxic-metabolic encephalopathy but is not specific to hepatic disease.

Asterixis is a clue to metabolic brain dysfunction, not a liver-specific reflex.

Stabilize, exclude, precipitant-hunt, then prevent recurrence

A reproducible sequence prevents anchoring on cirrhosis while missing sepsis, bleeding, stroke, or medication toxicity.

Assess airway, breathing, circulation, glucose, focal neurologic signs, medication or toxin exposure, and need for urgent neuroimaging.

Search for gastrointestinal bleeding, infection, constipation, dehydration, acute kidney injury, electrolyte disturbance, excess diuresis, sedatives, and nonadherence.

Start therapy when overt HE is clinically likely; do not delay treatment for an ammonia result.

Ammonia participates in biology but cannot run the diagnosis

Venous ammonia is vulnerable to collection and processing effects, overlaps across clinical grades, and may not track moment-to-moment cognition.

A high ammonia level is neither sufficient to diagnose HE nor reliable for grading severity or monitoring therapeutic response.

A normal ammonia value should prompt diagnostic reconsideration, especially when the presentation is atypical, but it does not substitute for a complete clinical evaluation.

Treatment success is judged by mental status, function, bowel regimen tolerance, precipitant control, and recurrence rather than normalization of ammonia.

Track nitrogen from gut to shunt to astrocyte

The anatomy explains why bowel therapy, liver failure, and TIPS all alter the same brain syndrome.

Gut nitrogenous substrates are converted into ammonia and other neurotoxins, which normally undergo hepatic detoxification.

Cirrhosis reduces hepatocellular clearance and creates spontaneous portosystemic collaterals; TIPS intentionally increases portal-systemic shunting.

In the brain, astrocyte glutamine accumulation, swelling, inflammation, and altered neurotransmission contribute to cognitive and motor dysfunction.

Lactulose treats the episode; rifaximin helps stop the cycle

Dosing must achieve efficacy without causing dehydration and electrolyte loss that themselves precipitate HE.

For overt HE, give lactulose and titrate to improvement followed by about 2 to 3 soft bowel movements daily; oral, nasogastric, or rectal routes can be selected according to safety.

Avoid over-catharsis. Diarrhea, hypovolemia, hypernatremia, hypokalemia, and acute kidney injury can worsen cognition and trigger another episode.

Rifaximin is typically added to lactulose to prevent recurrence after recurrent overt HE, while education addresses adherence, early warning signs, driving safety, nutrition, and precipitant avoidance.