Hepatic Encephalopathy

GI NOTES

Hepatic Encephalopathy

Key points

Hepatic encephalopathy (HE) is a clinical diagnosis of brain dysfunction caused by liver failure or portosystemic shunting, after excluding other causes.
Always look for and treat the precipitant: infection, GI bleeding, constipation, dehydration, electrolyte problems, AKI, sedatives.
Routine ammonia levels are not suggested to guide treatment (ACG 2026).
Lactulose is first line, titrated to 2 to 3 soft stools a day. Add rifaximin for acute overt HE and to prevent recurrence.
Do not restrict protein: aim for 1.2 to 1.5 g/kg/day plus a late-evening snack.

1. Classification

West Haven grade	Clinical features	Category
Minimal	Abnormal psychometric tests only	Covert
Grade 1	Trivial lack of awareness, short attention span, sleep inversion	Covert
Grade 2	Lethargy, disorientation to time, asterixis, inappropriate behavior	Overt
Grade 3	Somnolent but rousable, confused, disoriented to place	Overt
Grade 4	Coma	Overt

HE is also described by course (episodic, recurrent within 6 months, persistent) and by trigger (precipitated or spontaneous).

2. Evaluation

Diagnosis is clinical. Exclude hypoglycemia, intoxication, alcohol withdrawal, Wernicke encephalopathy, sepsis, stroke and seizures.
Ammonia: not suggested routinely to guide treatment. A single high value does not confirm HE, and levels do not track severity well.
Brain imaging: only for focal deficits, head trauma, or failure to improve with treatment.
Precipitant work-up: CBC, metabolic panel, glucose, cultures, diagnostic paracentesis if ascites, urinalysis, chest X-ray, medication review, rectal exam for bleeding.

3. Treating overt HE

FIGURE: MANAGEMENT OF AN EPISODE OF OVERT HE

Confusion in a patient with cirrhosis

Grade 3 or 4: protect the airway, ICU

Exclude other causes; check glucose

Find and treat the precipitant

Lactulose until 2 or more soft stools, then 2 to 3 per day (PEG 4 L is an alternative)

Add rifaximin 550 mg twice daily

Original diagram based on the ACG 2026 hepatic encephalopathy guideline.

Drug	Dose	Notes
Lactulose	About 25 mL (20 g) every 1 to 2 hours until a bowel movement, then titrate to 2 to 3 soft stools per day. Rectal enema if unable to take by mouth.	Over-purging causes dehydration, hypernatremia and AKI, which can worsen HE.
Polyethylene glycol (PEG 3350)	4 liters over 4 hours	Alternative to lactulose for acute overt HE
Rifaximin	550 mg twice daily	Add to lactulose for acute overt HE and for recurrence prevention
Zinc	Supplement if blood zinc is low	For persistent symptoms despite lactulose and rifaximin

4. Preventing recurrence

After a first episode: lactulose, adjusted using stool frequency and the Bristol stool scale.
Recurrent episodes on lactulose: add rifaximin.
Refractory HE with a large spontaneous portosystemic shunt and preserved liver function: consider shunt embolization.
Before elective TIPS in decompensated cirrhosis, start rifaximin 14 days before and continue at least 6 months.
Refer for liver transplant evaluation; HE is a sign of decompensation.
Counsel about driving and safety; even covert HE impairs driving.

5. Nutrition

Protein 1.2 to 1.5 g/kg/day; protein restriction worsens sarcopenia and does not shorten HE.
Energy 30 to 35 kcal/kg/day, with small frequent meals and a late-evening snack.
Branched-chain amino acid supplements if diet alone cannot meet protein needs.
Exercise to preserve muscle, which helps clear ammonia.

6. High-yield pearls

Constipation and over-diuresis are common, easily fixed triggers.
Benzodiazepines and opioids are frequent culprits; avoid them when possible.
Rifaximin is not a substitute for lactulose; it is an add-on.
Asterixis is not specific to HE; it also occurs in uremia and CO2 retention.

Self-check questions

Should you check an ammonia level to decide whether to treat HE?
Lactulose target?
When is rifaximin added?
Should protein be restricted in HE?

Answers: (1) No. HE is a clinical diagnosis, and routine ammonia is not suggested to guide treatment. (2) Two to three soft bowel movements per day. (3) For acute overt HE together with lactulose, and to prevent recurrence. (4) No. Aim for 1.2 to 1.5 g/kg/day.

References

ACG Clinical Guideline: Hepatic Encephalopathy. Am J Gastroenterol. 2026;121(3):588-618. doi:10.14309/ajg.0000000000003899.
Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the AASLD and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.
Bass NM, Mullen KD, Sanyal A, et al. Rifaximin Treatment in Hepatic Encephalopathy. N Engl J Med. 2010;362(12):1071-1081.
Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174(11):1727-1733.

For educational purposes only. This note does not replace clinical judgment or local protocols. Check doses against current labeling and institutional guidance.