Liver Lineup: What's New in the ACG Hepatic Encephalopathy Guideline

Welcome back to Liver Lineup: Updates & Unfiltered Insights!

Nancy Reau, MD, of Rush University Medical Center, and Kim Brown, MD, of Henry Ford, welcome Jasmohan Bajaj, MD, MS, of Virginia Commonwealth University and the Richmond VA Medical Center, to discuss the new American College of Gastroenterology (ACG) guideline on hepatic encephalopathy (HE). This first segment of a 3-part series covers what changed in diagnosis, inpatient care, and recurrence prevention.

How Does the New ACG Guideline Change Hepatic Encephalopathy Diagnosis in Clinic?

Bajaj opened by noting patients are older and more comorbid than a decade ago, which complicates what looks like HE. The guideline widens its focus to caregivers, finances, and a new social infrastructure axis, since a patient-only focus misses roughly 50% of the burden, he said.¹

It also adds structured steps for three conditions capable of mimicking or worsening HE. Alcohol use, obstructive sleep apnea, and mild cognitive impairment or dementia each get a defined clinic check. Bajaj noted most sleep disturbance in patients with cardiometabolic disease now traces to sleep apnea, not HE, and he wants to avoid labeling those patients with HE and committing them to lactulose for life. He has described the covert stage as often ignored or confused for overt disease.²

For clinic workflow, Bajaj pointed to the AUDIT-C, which takes about 2 minutes, the STOP-BANG for suspected sleep apnea, and the Mini-Mental State Examination, a rarer positive.

On ammonia, Bajaj was direct. Levels rise in cirrhosis, so a high value in an alert, asymptomatic outpatient does not establish HE, and ammonia alone should neither diagnose nor exclude it.¹ HE remains a clinical diagnosis of exclusion built on patient report and caregiver observations such as near misses, car accidents, and trouble at work.

When other causes are excluded and symptoms persist, the guideline outlines a theragnostic lactulose trial. Bajaj advised starting at a low dose, titrating by the Bristol stool scale to avoid gas and excess stools, and reassessing in person at roughly eight weeks. He estimated about 80% of patients improve and 10% to 15% fail a true trial. For those patients, he suggested neuropsychology referral through primary care, stopping lactulose, and removing the HE diagnosis from the chart because of possible medicolegal consequences.

How Should Hospitalized Patients With Hepatic Encephalopathy Be Managed, and When Should Rifaximin Start?

Brown noted inpatient teams recognize HE more readily because cirrhosis is already known. Bajaj reiterated the guideline's call to look past HE for other causes, including alcohol and stroke. Once HE is suspected, priorities include preventing aspiration pneumonia and hypernatremia, with grade 3 or higher encephalopathy ideally managed in a monitored setting.

Precipitants are also shifting. Bajaj said acute kidney injury and infection now outpace GI bleeding as common triggers. Identifying the trigger is the second step, followed by therapy.

The notable change from prior AASLD and EASL guidance is earlier rifaximin alongside lactulose in the inpatient setting, because patients tolerate it and the combination may work better than lactulose alone.¹ For grade 3 episodes, Bajaj favored lactulose enemas over oral dosing, which risks aspiration.

Because specialists often see patients a day or two after admission, Bajaj urged teaching ED, house, and support staff the basics. These include timely paracentesis to exclude spontaneous bacterial peritonitis, monitored or ICU transfer for grade 3 or higher, and early lactulose. ACG guidelines come with a one-page handout distilling the critical points for posting on units.

How Can Clinicians Prevent Recurrent Hepatic Encephalopathy and Avoid Readmission?

Reau asked what the guideline recommends after the patient clears. Bajaj called recurrence prevention the most important part of HE care and the reason the guideline added social infrastructure as a fifth axis. He estimated 95% of HE admissions could be preventable with 10 to 15 extra minutes spent with the patient, caregiver, family, and pharmacist.

After a first episode, Bajaj recommended a family meeting. He described a recent 35-minute session for a 75-year-old patient and noted the discussion is far harder when the patient is a working breadwinner who drives. Families should learn early warning signs so they do not wait until the patient is comatose, decide whether they are comfortable titrating lactulose, and clarify who checks on a patient living alone.

If the patient has not fully recovered, Bajaj advised at least one CT or MRI, rather than the ultrasound used for HCC surveillance, to look for spontaneous portosystemic shunts. Patients who recur despite adherence and have a relatively low MELD score are candidates for embolization. He added transplant listing deserves consideration at the first episode, given

Editors’ note: Relevant disclosures for Reau include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for Brown include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for Bajaj include Bausch/Salix, Grifols, Cosmo, and others.

References

1. Bajaj JS, Jakab SS, Jesudian AB, et al. ACG clinical guideline: hepatic encephalopathy. Am J Gastroenterol. 2026;121(3):588-618. doi:10.14309/ajg.0000000000003899

2. Hillenbrand A. ACG issues new hepatic encephalopathy guidelines for diagnosis, treatment, nutrition, and transplant, with Jasmohan Bajaj, MD, MS. HCPLive. March 24, 2026. Accessed October 9, 2026. https://www.hcplive.com/view/acg-issues-new-hepatic-encephalopathy-guidelines-for-diagnosis-treatment-nutrition-and-transplant-with-jasmohan-bajaj-md-ms-