New American College of Gastroenterology guidelines on hepatic encephalopathy: What's changing in diagnosis, treatment, and prevention

In March 2026, the American College of Gastroenterology published new clinical guidelines on hepatic encephalopathy in The American Journal of Gastroenterology. The document was prepared by a group of authors led by Jasmohan S. Bajaj and colleagues. The guidelines present 24 recommendations for the diagnosis, treatment, and prevention of this complication of liver cirrhosis. [1]

The authors immediately establish an important framework: hepatic encephalopathy is not a minor symptom, but one of the most severe and burdensome complications of cirrhosis. It impacts not only the risk of hospitalization and mortality, but also the daily life of the patient and family, their ability to work, drive, adhere to treatment, and promptly recognize deterioration. [2]

The new version of the guidelines emphasizes not only the overt but also the latent form of the disease. This is important because minimal and latent hepatic encephalopathy are often underestimated: the patient may not yet appear "severe," but may already be losing concentration, reaction time, and quality of life. Therefore, the new recommendations place significant emphasis on testing, outpatient prevention, nutritional support, and special situations, including bypass surgery and transplantation. [3]

At a practical level, this guideline is also important because it updates an old paradigm. Previous international documents on hepatic encephalopathy already discussed lactulose, rifaximin, and the role of clinical assessment, but the 2026 version more firmly articulates several key points: not relying on ammonia as a diagnostic guideline alone, not restricting protein, more actively addressing sarcopenia, and more clearly considering prophylaxis after transjugular intrahepatic portosystemic shunting. [4]

Table 1. Passport of the new recommendation

Parameter	Data
Organization	American College of Gastroenterology
Magazine	The American Journal of Gastroenterology
Date of publication	March 3, 2026
Volume and issue	121, issue 3
Pages	679-688
Number of recommendations	24
Main topics	diagnostics, inpatient treatment, relapse prevention, nutrition, sarcopenia, special situations
DOI	10.14309/ajg.0000000000003899

Source of the table: official announcement, article metadata and publication card. [5]

Why is this update important?

Hepatic encephalopathy is a complication of cirrhosis, which disrupts brain function due to liver failure and portosystemic shunting. In practice, this can manifest as forgetfulness, absentmindedness, sleep disturbances, slowness, tremors, disorientation, drowsiness, and, in severe cases, stupor or coma. The problem is that early forms are often subtle and therefore missed. [6]

The authors of the new document also emphasize the broader significance of the problem: the transition from latent to overt disease is not fully reflected in current criteria for inclusion on the transplant waiting list. In other words, for some patients, quality of life, cognitive function, and daily safety are already seriously impaired, but this does not always formally give them sufficient priority. This is an important signal for clinicians working with decompensated cirrhosis. [7]

The update is also important because of the practical differences between "traditional" logic and the modern approach. Previously, many clinical decisions in real-world practice were based on ammonia levels, protein restriction, and the rather delayed initiation of preventive therapy. The new guidelines, in contrast, advocate a more clinical approach: looking at symptoms, risk factors, relapses, nutritional status, and sarcopenia, and only then interpreting laboratory results in the overall context. [8]

This is also a significant change for patients and families. The guidelines effectively recognize that hepatic encephalopathy is not just an intensive care unit problem. It is a chronic condition with a risk of recurrent episodes, impacting daily safety, the ability to drive, operate machinery, and adequately assess one's own condition. Therefore, the new version places significantly more emphasis on outpatient monitoring and relapse prevention. [9]

Table 2. What's new and highlighted in the 2026 version

Direction	The focus of the new recommendation
Hidden and minimal form	a 1-test strategy is proposed rather than a combination of 2 tests
Ammonia	It is not recommended to use this indicator alone for diagnosis or routine treatment.
Inpatient treatment	lactulose remains the base, polyethylene glycol is considered as an alternative, rifaximin is added to lactulose
Relapse prevention	outpatient first-line lactulose, rifaximin is added to prevent recurrences
Nutrition	against protein restriction, target protein 1.2-1.5 g/kg/day
Sarcopenia	the role of exercise and late evening snacks is emphasized
TIPS	rifaximin 14 days before planned bypass surgery and up to 6 months after in patients with decompensated cirrhosis
Transplantation	In case of multiple episodes and MELD <15, it is suggested to evaluate the possibility of a living donor

Table source: official ACG Guideline Highlights file. [10]

What is changing in diagnostics?

One of the most notable news items is the approach to occult and minimal hepatic encephalopathy. The guidelines propose using a single-test strategy instead of a combination of two tests when assessing for minimal or occult hepatic encephalopathy. This appears to be a move toward greater practicality: physicians need a simpler and more applicable algorithm that can be used in a real-world setting, not just in a research center. [11]

However, this recommendation does not mean simplifying the diagnosis to a formality. Official materials list testing options that can be used for latent and minimal forms of the disease: the Psychometric Hepatic Encephalopathy Score, Animal Naming Test, Stroop EncephalApp, and Critical Flicker Frequency. In other words, the emphasis shifts from an "easy" diagnosis to a more rational choice of instrument. [12]

Another fundamental point concerns ammonia. The authors do not recommend diagnosing hepatic encephalopathy based solely on ammonia levels. Furthermore, routine use of ammonia in hospital settings to guide treatment decisions is not recommended. The ACG file explicitly states that this indicator fluctuates significantly throughout the day, is not very reliable, and correlates poorly with the severity of hepatic encephalopathy. Its usefulness is rather the opposite: a normal value can help cast doubt on the diagnosis. [13]

Finally, the new guidelines attempt to reduce unnecessary diagnostic testing. The document emphasizes that isolated asterixis without changes in behavior or alertness is insufficient to diagnose overt hepatic encephalopathy. Routine neuroimaging is also not recommended for patients with cirrhosis and confusion without focal neurological deficits. This is an important warning against automatically ordering unnecessary tests without clinical justification. [14]

Table 3. Main diagnostic shifts

Question	New ACG position
How to test hidden or minimal form	prefer strategy 1 test
Can ammonia be used to diagnose?	No, ammonia itself is not enough.
Is it necessary to routinely repeat ammonia in hospital to adjust treatment?	No, it is not recommended
Is isolated asterixis sufficient for the diagnosis of overt asterixis?	No
Do all patients with confusion need a CT or MRI scan?	No, it is not routinely recommended without focal neurological deficit.
What tests are mentioned in the ACG materials?	PHES, Animal Naming Test, Stroop EncephalApp, Critical Flicker Frequency

Table source: ACG official materials and summary of recommendations. [15]

What is changing in treatment and relapse prevention?

In hospitals, lactulose remains the mainstay of treatment for overt hepatic encephalopathy. This isn't a revolution, but a confirmation of the old standard. However, the new document emphasizes that lactulose is needed not only to relieve an acute episode but also to improve hospitalization outcomes and reduce the risk of recurrent episodes. In other words, the drug has been firmly established as a mainstay in both acute and preventive strategies. [16]

The guidelines also add an important alternative: high-volume polyethylene glycol preparations can be used as an alternative to lactulose in hospitalized patients with overt hepatic encephalopathy. This is a useful practical point for clinicians, as it does not mean completely eliminating lactulose, but rather providing an additional viable option in the hospital. [17]

The role of combination therapy is particularly emphasized. In acute situations, rifaximin is proposed as an adjunct to lactulose. And in outpatient prophylaxis in patients with cirrhosis and a history of overt hepatic encephalopathy, rifaximin is also proposed to prevent relapses. This reinforces the concept: lactulose remains the foundation, while rifaximin becomes a key enhancer in more severe or recurrent cases. [18]

To prevent recurrent episodes after the initial case of overt hepatic encephalopathy, lactulose is recommended as first-line outpatient therapy. Official ACG guidelines also specify a practical titration guideline: 2-3 soft stools per day, recommending the use of not only stool frequency but also the Bristol Stool Form Chart. This is an important detail, as titration errors often render treatment either ineffective or overly aggressive. [19]

Another small but interesting piece of news is the mention of zinc. The Guideline Highlights file indicates that zinc supplementation can be considered in patients who continue to relapse despite treatment with lactulose and rifaximin. This doesn't seem like a new, one-size-fits-all therapy, but it does indicate that the guidelines allow for additional steps in difficult patients who don't respond to the standard regimen. [20]

Table 4. Drug strategy according to the new recommendation

Clinical situation	Approach
A hospitalized patient with overt hepatic encephalopathy	lactulose is recommended
Stationary alternative	polyethylene glycol can be used as an alternative
Acute episode in hospital	rifaximin is added to lactulose
After the first episode of overt form, outpatient	lactulose 1st line
The purpose of lactulose titration	2-3 soft stools per day
Recurrent encephalopathy due to cirrhosis	add rifaximin for prophylaxis
Recurrent relapses despite lactulose and rifaximin	zinc can be considered

Table source: ACG official materials and review of available guidelines. [21]

Nutrition, sarcopenia, TIPS and transplantation: the most practical block

One of the strongest sections of the new recommendation is devoted to nutrition and sarcopenia. The document recommends a target protein level of 1.2-1.5 g/kg body weight per day, a late evening snack for patients with cirrhosis, and exercise as part of the management strategy. This is an important signal against the outdated fear of protein in these patients. [22]

Particularly significant is the fact that the guidelines explicitly advise against protein restriction in patients with hepatic encephalopathy. For clinical practice, this is one of the document's most useful insights. The old intuitive approach seemed simple: less protein, less ammonia. But modern understanding shows that protein restriction can exacerbate muscle loss, and sarcopenia itself worsens ammonia metabolism and the course of encephalopathy. [23]

A separate section concerns patients undergoing transjugular intrahepatic portosystemic shunting. Official ACG guidelines recommend initiating rifaximin 14 days before planned TIPS and continuing it for up to 6 months in patients with decompensated cirrhosis. They also mention embolization of extrahepatic collaterals. This makes the TIPS block much more prophylactic than in older regimens, where the physician often responded to encephalopathy that had already developed. [24]

Finally, the document also includes a transplantation signal. The Guideline Highlights file states that patients with multiple episodes of hepatic encephalopathy and a MELD <15 should be considered for living donor transplantation. This is an important extension of clinical thinking: even with a relatively low MELD, recurrent encephalopathy can seriously impair the patient's life and safety. [25]

Table 5. Practical non-drug emphases

Direction	What does ACG recommend?
Protein	do not limit
Target protein	1.2-1.5 g per kg per day
Late evening snack	recommended for patients with cirrhosis
Exercises	recommended as part of the management of sarcopenia
Risk after TIPS	thoughtful prevention before and after the intervention
Rifaximin in the context of TIPS	start 14 days before scheduled TIPS
Duration after TIPS	continue for up to 6 months in patients with decompensated cirrhosis
Transplantation	in case of multiple episodes and MELD <15, consider the living donor option

Table source: ACG Guideline Highlights. [26]

What does this mean for practice now?

The main conclusion of the new guidelines can be summarized simply: hepatic encephalopathy can no longer be viewed as an episodic problem "only during severe decompensation." This condition must be identified earlier, treated more systematically, and prevented more actively. The emphasis has shifted from reactive to proactive medicine. [27]

For the physician, this means three things. First, don't rely mechanically on ammonia and be mindful of the clinical picture. Second, don't underestimate the latent form in patients with complaints of concentration, decreased quality of life, hypoalbuminemia, decompensated cirrhosis, portosystemic shunts, or work where cognitive impairment is particularly dangerous, such as in drivers and pilots. Third, actively use outpatient relapse prevention. [28]

For the patient and family, this means something equally important. Treatment should not be reduced to the phrase "drink syrup until you feel better." The new logic includes monitoring stool and its shape, nutritious nutrition, preventing muscle wasting, assessing household safety, early recognition of cognitive decline, and discussing the further trajectory of the disease, including TIPS and transplantation, when appropriate. [29]

This is precisely why this guideline can be considered one of the most practically oriented publications on the topic in recent years. It not only confirms the role of lactulose and rifaximin, but also repackages the management of hepatic encephalopathy in a more modern model: less laboratory fetishism, more clinical thinking, nutritional support, prevention, and attention to quality of life. [30]

News source

Bajaj JS, Jakab SS, Jesudian AB, Rahimi RS, Duarte-Rojo A, Chen PH, Wong RJ, Tapper EB, Tandon P. ACG Clinical Guideline: Hepatic Encephalopathy. The American Journal of Gastroenterology. 2026;121(3):679-688. DOI: 10.14309/ajg.0000000000003899.