What Is the Current Approach to Hepatic Encephalopathy?

HE is a syndrome, not a laboratory value

Ammonia contributes to HE pathophysiology but serum levels correlate imperfectly with clinical severity. The 2026 ACG guideline explicitly discourages routine ammonia monitoring to make inpatient treatment decisions. A normal ammonia in a confused patient with cirrhosis should increase suspicion for another diagnosis rather than being ignored.

Look for precipitants every time

Common precipitants include infection, GI bleeding, constipation, excess diuresis or dehydration, electrolyte abnormalities, renal dysfunction and medications that suppress the central nervous system. Treating the precipitant is often as important as increasing lactulose.

Lactulose remains the foundation

Lactulose improves outcomes in overt HE and is also first-line outpatient prophylaxis after an episode. Titrate to a practical stool target—commonly 2-3 soft bowel movements daily—while avoiding severe diarrhea, dehydration and hypernatremia. The Bristol Stool Scale may help patients and caregivers titrate more consistently.

Rifaximin is an add-on, not a replacement for basic care

The strongest outpatient role is prevention of recurrent HE, particularly when episodes occur despite lactulose. The 2026 ACG guideline also supports adding rifaximin to lactulose in acute overt HE for incremental benefit. Access and cost remain practical barriers.

When improvement is poor, reconsider the diagnosis

If mental status has not meaningfully improved after 48-72 hours of adequate therapy and reversal of precipitants, evaluate for alternative neurologic/metabolic causes and consider large spontaneous portosystemic shunts. Routine brain imaging is not required in uncomplicated HE, but focal deficits, seizures, trauma or atypical features change that decision.

A practical clinical approach

1. Grade mental status clinically and assess airway/safety needs.
2. Search systematically for bleeding, infection, medication effects, constipation, dehydration, renal dysfunction and electrolyte disturbance.
3. Treat with lactulose and correct the precipitant.
4. Add rifaximin in appropriate acute or recurrent disease.
5. Do not chase ammonia levels as a treatment target.
6. If response is inadequate, reconsider alternate diagnoses, shunts and transplant implications.

Common errors to avoid

• Treating a high ammonia level instead of the patient.
• Giving escalating lactulose until severe diarrhea causes dehydration.
• Missing infection or GI bleeding as the precipitant.
• Continuing benzodiazepines or other sedating drugs when alternatives exist.
• Failing to provide caregivers a clear recurrence-prevention plan.

What should trainees remember?

HE is a clinical diagnosis and a recurrent-risk condition. The best care combines precipitant reversal, lactulose-based therapy, rational rifaximin use and structured prevention after discharge.

Free further reading from Dr. Alan B. R. Thomson

See Dr. Thomson's Guideline-Based Management in Hepatology and Clinical Pharmacology for background on cirrhosis complications and pharmacologic management.

Frequently asked questions

Should ammonia levels be followed to judge treatment response?

No. Clinical response should guide management; routine serial ammonia testing is not recommended.

What is the lactulose target?

Commonly 2-3 soft bowel movements daily, avoiding dehydration.

When should rifaximin be added?

It is strongly used for recurrent overt HE despite lactulose and may add benefit during acute overt HE.

References

1. Thomson ABR. Guideline-Based Management in Hepatology. CAPstone Academic Publishers; 2015. ISBN 978-1502928078.

2. Thomson ABR. Clinical Pharmacology, Physiology and Pathophysiology: Gastroenterology, Hepatology, and Pancreaticobiliary Disorders. CAPstone Academic Publishers; 2024. ISBN 979-8323955770.

3. Bajaj JS, Jakab SS, Jesudian AB, et al. ACG Clinical Guideline: Hepatic Encephalopathy. Am J Gastroenterol. 2026;121:588-618.

4. Sierra L, Duong N. From Confusion to Clarity: A Practical Guide to Hepatic Encephalopathy. Evidence-Based GI. 2026.