ACG Issues New Hepatic Encephalopathy Guidelines For Diagnosis, Treatment, Nutrition, and Transplant, With Jasmohan Bajaj, MD, MS,

Recently, the American College of Gastroenterology (ACG) issued 24 new clinical recommendations for diagnosing, managing, and preventing hepatic encephalopathy (HE).

For diagnosis, the guidelines recommend against using ammonia alone to diagnose MHE/CHE or guide treatment decisions, against ordering routine brain imaging in cirrhosis patients with confusion unless there are new focal neurologic deficits, and advise always screening for mimics, including sleep apnea, alcohol-related conditions, and mild cognitive impairment.

For treatment, lactulose remains first-line, titrated to 2–3 soft bowel movements daily using the Bristol Stool Scale. PEG (4L) is a reasonable alternative to lactulose in acute OHE. Rifaximin should be added to lactulose in acute OHE, don't wait for lactulose to fail, and should be started 14 days before elective TIPS and continued for at least 6 months.

For nutrition, the guidelines recommend against protein restriction, noting it worsens outcomes, and target 1.2–1.5 g/kg/day protein, or up to 2 g/kg/day in critically ill patients. A late-night snack is recommended, as is BCAA supplementation if protein needs cannot be met through diet alone. Exercise is beneficial despite transient ammonia rises.

For discharge and follow-up, medication reconciliation at discharge is essential, with a review of opiates, benzodiazepines, gabapentin, PPIs, and sleep aids. All patients should receive written and oral advice against driving within 3 months of an OHE episode, and caregivers should be screened for burnout.

For transplant, living donor transplant should be considered for patients with multiple HE episodes even if MELD is below 15, and adding 4–5 MELD points more accurately reflects true 90-day mortality risk in these patients.

These guidelines experts utilized the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process to evaluate evidence quality, additionally highlighting additional key concept statements.

HCPLive spoke with an expert who helped formulate the guidelines, Jasmohan Bajaj, MD, MS, Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition at Virginia Commonwealth University and Richmond VA Medical Center in Richmond, VA.

HCPLive: This is the first major ACG update on hepatic encephalopathy in a couple of years. From your perspective, what are the most practice-changing updates clinicians should be aware of right away?

Bajaj: Thank you for shining a spotlight on hepatic encephalopathy, and we are so happy that the college was also able to commission this guideline. The most practice-changing updates are: The first is that minimal or covert hepatic encephalopathy is an entire pre-clinical stage that is often not only ignored but confused for actual hepatic encephalopathy — we are missing things such as dementia, alcohol effects, or obstructive sleep apnea, and falsely diagnosing overt hepatic encephalopathy. Comorbid conditions are important. Ammonia has been given a lot of importance as the sole diagnostic and prognostic marker, and we need to get away from that. Ammonia should be one of many things, if at all, that informs our decision on whether someone has hepatic encephalopathy and how well or badly they're doing. Inpatient management of hepatic encephalopathy is critical, we want to make sure patients do not develop aspiration pneumonia, that they get treated very quickly, and that they are not discharged too soon before they and their family members are able to understand what actually happened and what the risks of recurrence are. We also added a concept called social infrastructure, because hepatic encephalopathy is not only a disease of the patient, it's a disease of the entire family and their ecosystem. A lot of these patients are not being counseled appropriately or to the extent that we are comfortable they understand the need for medications, medication affordability, and other details that require a deep social insight into what the patient and their family members are feeling. Prevention of recurrence is also important, ensuring patients have good contacts through apps, and making sure patients are not overdosed on lactulose. We often have blanket ways of prescribing lactulose, which frequently has very adverse GI side effects, causing some people to stop taking it prematurely. We have recommended use of the Bristol Stool Scale, which tells you the quality of stool and not just the quantity, giving control back to patients and their caregivers to judge how much lactulose they actually need to take. Initiating rifaximin for secondary prophylaxis has not changed but remains important. And last but not least, ensuring these patients are connected to someone who can consider them for a liver transplant, particularly patients with recurrent hepatic encephalopathy episodes but a low MELD score, for whom living donor transplant should be considered.

HCPLive: Despite these updated recommendations, where do you see the biggest unmet needs in HE, whether in diagnostics, therapeutics, or care delivery, and what should clinici ans watch for next?

Bajaj: The important unmet needs are the underdiagnosis of covert or minimal hepatic encephalopathy, because those patients are still suffering, and we need to ensure we have the ability to exclude other comorbid conditions that our patients are unfortunately already prone to. The other unmet need is ensuring that patients are discharged properly — that the discharge handoff after an inpatient hepatic encephalopathy episode is done to the point where we are comfortable that the patients, their family members, and everyone involved understands what happened. This is very unique to each medical system, so one size does not fit all. And last but not least, ensuring that these patients get a fair shake when it comes to liver transplant — because with every hepatic encephalopathy episode, the brain develops further injury. Time is brain in hepatic encephalopathy as well, and we have to come up with ways to diagnose hepatic encephalopathy that can satisfy transplant boards to give patients extra points or consideration for a living donor transplant.

HCPLive: Are there any other aspects of the guidelines you'd like to highlight — perhaps around nutrition or the role of ammonia testing — that clinicians may still be getting wrong in practice?"

Bajaj: I'd like to speak to both ammonia and protein. On nutrition, patients with cirrhosis are usually protein deficient, and even though they might be obese, they could be sarcopenic, meaning they have less functional muscle available to help improve systemic inflammation and clear ammonia from circulation. We want to use a combination of careful nutrition and exercise to ensure sarcopenia is addressed, and that means absolutely no protein restriction. The proteins with the least ammoniagenesis are typically vegetarian and dairy proteins compared to red meat, but you have to see what the patient actually eats, and that's where knowledge of social infrastructure comes in. What the patient can afford is also important. Another important point for the prevention of sarcopenia is a late-night snack — a mixture of carbohydrates and protein that prevents muscle loss overnight, because patients with cirrhosis have problems with gluconeogenesis during fasting. On ammonia, while ammonia is central to the pathogenesis of hepatic encephalopathy, where things get lost in translation is figuring out whether ammonia levels drawn from venous or arterial blood accurately reflect the stage of confusion or hepatic encephalopathy the patient is in, and whether checking them repeatedly adds anything beyond what we already know clinically. Patients with cirrhosis need ammonia levels checked very infrequently, if at all, and those levels should be interpreted in the light of your clinical judgment. In other words, no one who is alert and oriented with cirrhosis should be treated just for a high ammonia level, you should be treating the patient, not their lab value.

Bajaj reports relevant disclosures with Bausch/Salix, Grifols, Cosmo, and others.

References

1. Bajaj JS, Jakab SS, Jesudian AB, et al. ACG Clinical Guideline: Hepatic Encephalopathy. American Journal of Gastroenterology. 2026;121(3):588-618. doi:https://doi.org/10.14309/ajg.0000000000003899
2. ‌ACG Hepatic Encephalopathy Guideline Summary - Guideline Central. Guidelinecentral.com. Published 2026. Accessed March 24, 2026. https://www.guidelinecentral.com/guideline/5115195/#section-5115242

‌