HE Is a Major Neuropsychiatric Complication of Cirrhosis¹

What causes HE?

Poor liver function leads to the accumulation of gut-derived neurotoxins (eg, ammonia), disrupting normal brain activity^1,2

Precipitating factors can trigger an HE episode, including³:

Infection

GI bleeding

Electrolyte issues

Constipation

Diuretic overdose

How does HE present?

HE has a range of mental and physical symptoms, with overt HE causing more severe impairment that often requires hospitalization³
West Haven Criteria (Conn Score) can be used to grade HE symptoms³

West Haven CRITERIA (Conn Score)

COVERT HE

Minimal

No observable symptoms
Detectable only by psychometric testing

Grade I

Euphoria or anxiety
Trivial lack of awareness
Shortened attention span
Impaired ability to add/subtract
Altered sleep rhythm

OVERT HE

Grade II

Lethargy or apathy
Disorientation for time
Personality change and/or inappropriate behavior
Dyspraxia
Asterixis

Grade III

Somnolence to semi-stupor
Confusion
Responsive to stimuli
Gross disorientation
Bizarre behavior

Grade IV

Coma

Up to 80% of patients with cirrhosis will develop covert HE,

and up to40%will have an overt HE episode³

What are the healthcare burdens of overt HE?

The prevalence of overt HE has been increasing over time⁴

In 2020, 21% of patients with cirrhosis had an overt HE episode (vs 13% in 2007)⁴*

*Data from MarketScan Commercial Claims and Encounters Database (2007-2020) and 100% Medicare Research Identifiable (RIF) database (2007-2020). Both databases include information on enrollment, diagnoses/procedures, and costs of treatments and medical services. Adult patients with cirrhosis (≥65 years for Medicare) and hepatic encephalopathy were identified based on the International Classification of Diseases, Ninth/Tenth Revision (ICD-9 /-10) and were required to have continuous health plan enrollment for the entire calendar year.⁴

Among patients hospitalized for overt HE, the median length of stay was 9 days (vs 6 days for all decompensation events)⁵

$11.9 billion—estimated inpatient charges associated with HE hospitalizations^6†

*Data from US National Inpatient Sample (2010-2014) of adults hospitalized with HE listed as a diagnosis (using ICD-9-CM code) at time of discharge.⁶

Once overt HE occurs, patients have an increased risk of recurrence³

~32% of patients hospitalized with overt HE were readmitted within 30 days^7‡

^‡Study utilized the 2013 Nationwide Readmission Database, representing ~49% of the US population and all hospitalizations, and focused particularly on hospitalized patients with HE (n=24,473) to assess independent predictors of 30-day readmission.⁷

Multiple episodes of overt HE can lead to persistent cognitive deficits in working memory, response inhibition, reaction time, and attention span⁸
Compared to other cirrhosis complications, patients with overt HE have significantly decreased survival rates^9,10

*Data from 3 Danish healthcare registries of patients with cirrhosis due to alcohol use disorder and not previously examined for suspected cirrhosis (N=466) diagnosed between January 1, 1993, and August 31, 2005. The diagnosis of HE was based on the patient’s clinical presentation, usually supported by the blood ammonia level and/or a continuous reaction time. Minimal HE was excluded. Values represent survival probabilities after diagnosis of the complication, with or without development of additional complications.¹⁰

Delayed recognition and management of HE may lead to worse outcomes¹¹

What should I consider when screening for HE?

HE symptom assessments should be performed routinely, especially in patients with a previous episode or risk factors¹²

The diagnosis of overt HE should be based on clinical evaluation, including¹²:

Check for physical signs of chronic liver disease and HE during the physical examination, such as asterixis, extrapyramidal dysfunction, hyperreflexia, and slow speech

Patients with lower grades of overt HE may require use of neuropsychological tests (eg, PHES test) to help establish cognitive dysfunction

In patients with marked altered consciousness, the Glasgow Coma Scale and related tests can be used to help assess the extent of consciousness deficits

Grading severity of symptoms using the West Haven Criteria³

Ruling out similar conditions (eg, stroke, electrolyte disturbances, diabetes complications, or drug/alcohol intoxication)^3,12

Evaluating malnutrition³

Identifying precipitating factors^3,12,13

In one study,
caregivers were shown to have helped identify 25% of overt HE episodes¹⁴

Download the HE Diagnostic Tips Guide

HE Diagnostic Tips

What do current guidelines recommend for overt HE management?

AASLD/EASL Practice Guideline: Hepatic Encephalopathy in CLD

Access the HE Management Guideline

HE Management Guideline

Prompt management of an overt HE episode should include³:
Correction of precipitating factors
Use of nonabsorbable disaccharides, such as lactulose, to resolve the episode and help prevent recurrent episodes
Use of an add-on therapy to reduce the risk of HE recurrence in patients who have a recurrence while on lactulose alone
Patients should be well nourished and receive adequate protein in their diet, as loss of muscle and malnutrition are risk factors for overt HE³

How should I counsel a patient (and/or the caregiver of a patient) who is at risk of having overt HE or after they are hospitalized from an episode?

Discuss the need to reduce potential confounding and precipitating factors, including alcohol use³
Review their current medications and inform them of any potential risks¹⁵
Ensure sufficient understanding of the risks and associated symptoms of HE
Instruct on proper use of pharmacologic therapy to help prevent overt HE recurrence³
- Reinforce the need for medication adherence
- Review potential side effects and the need to titrate lactulose to prevent dehydration, which can precipitate an overt HE episode
Continue monitoring neurologic symptoms³
Provide nutritional management³

AASLD, American Association for the Study of Liver Diseases; ALD, alcohol-associated liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CLD, chronic liver disease; EASL, European Association for the Study of the Liver; ELF, enhanced liver fibrosis; FIB-4, fibrosis-4 index; GI, gastrointestinal; HE, hepatic encephalopathy; MASH, metabolic dysfunction–associated steatohepatitis; MASLD, metabolic dysfunction–associated steatotic liver disease; MELD, model of end-stage liver disease; PHES, Psychometric Hepatic Encephalopathy Score.

References

1. Garcia-Tsao G. In: Goldman L et al, eds: Goldman-Cecil Medicine. 26th ed. Elsevier; 2016:990-8.e3. 2. Bajaj JS et al. Am J Physiol Gastrointest Liver Physiol. 2012;3202(1):G168-G175. 3. Vilstrup H et al. Hepatology. 2014;60(2):715-735. 4. Wong RJ et al. Clin Transl Gastroenterol. 2025;16(5):e00823. 5. Ifrah A et al. Dig Dis Sci. 2024;69(9):3220-3225. 6. Hirode G et al. Dig Dis Sci. 2019;64(6):1448-1457. 7. Kruger AJ et al. Ann Hepatol. 2019;18(2):310-317. 8. Bajaj JS et al. Gastroenterology. 2010;138(7):2332-2340. 9. Bajaj JS et al. Clin Gastroenterol Hepatol. 2017;15(4):565-574. 10. Jepsen P et al. Hepatology. 2010;51(5):1675-1682. 11. Ventura-Cots M et al. Therap Adv Gastroenterol. 2018;11:1756283X17743419. 12. Shawcross DL et al. Eur J Gastroenterol Hepatol. 2016;28(2):146-152. 13. Kumral D et al. J Hosp Med. 2019;14(3):157-160. 14. Landis CS et al. Dig Dis Sci. 2016;61(6):1728-1734. 15. Williams S et al. United European Gastroenterol J. 2021;9(2):193-202.

HE Is a Major Neuropsychiatric Complication of Cirrhosis¹

What causes HE?

Poor liver function leads to the accumulation of gut-derived neurotoxins (eg, ammonia), disrupting normal brain activity^1,2

Precipitating factors can trigger an HE episode, including³:

How does HE present?

West Haven CRITERIA (Conn Score)

COVERT HE

Minimal

Grade I

OVERT HE

Grade II

Grade III

Grade IV

Up to 80% of patients with cirrhosis will develop covert HE,

and up to40%will have an overt HE episode³

What are the healthcare burdens of overt HE?

Delayed recognition and management of HE may lead to worse outcomes¹¹

What should I consider when screening for HE?

HE symptom assessments should be performed routinely, especially in patients with a previous episode or risk factors¹²

Check for physical signs of chronic liver disease and HE during the physical examination, such as asterixis, extrapyramidal dysfunction, hyperreflexia, and slow speech

Gathering patient history (including from caregivers) and performing a physical examination^3,12-14

Patients with lower grades of overt HE may require use of neuropsychological tests (eg, PHES test) to help establish cognitive dysfunction

In patients with marked altered consciousness, the Glasgow Coma Scale and related tests can be used to help assess the extent of consciousness deficits

Assessing mental status and sleep alterations^3,12

In one study,
caregivers were shown to have helped identify 25% of overt HE episodes¹⁴

Download the HE Diagnostic Tips Guide

What do current guidelines recommend for overt HE management?

AASLD/EASL Practice Guideline: Hepatic Encephalopathy in CLD

Access the HE Management Guideline

How should I counsel a patient (and/or the caregiver of a patient) who is at risk of having overt HE or after they are hospitalized from an episode?

References

HE Is a Major Neuropsychiatric Complication of Cirrhosis1

What causes HE?

Poor liver function leads to the accumulation of gut-derived neurotoxins (eg, ammonia), disrupting normal brain activity1,2

Precipitating factors can trigger an HE episode, including3:

How does HE present?

West Haven CRITERIA (Conn Score)

COVERT HE

Minimal

Grade I

OVERT HE

Grade II

Grade III

Grade IV

Up to 80% of patients with cirrhosis will develop covert HE,

and up to40%will have an overt HE episode3

What are the healthcare burdens of overt HE?

Delayed recognition and management of HE may lead to worse outcomes11

What should I consider when screening for HE?

HE symptom assessments should be performed routinely, especially in patients with a previous episode or risk factors12

Gathering patient history (including from caregivers) and performing a physical examination3,12-14 Check for physical signs of chronic liver disease and HE during the physical examination, such as asterixis, extrapyramidal dysfunction, hyperreflexia, and slow speech

Gathering patient history (including from caregivers) and performing a physical examination3,12-14

Assessing mental status and sleep alterations3,12

In one study, caregivers were shown to have helped identify 25% of overt HE episodes14

Download the HE Diagnostic Tips Guide

What do current guidelines recommend for overt HE management?

AASLD/EASL Practice Guideline: Hepatic Encephalopathy in CLD

Access the HE Management Guideline

How should I counsel a patient (and/or the caregiver of a patient) who is at risk of having overt HE or after they are hospitalized from an episode?

References

HE Is a Major Neuropsychiatric Complication of Cirrhosis¹

Poor liver function leads to the accumulation of gut-derived neurotoxins (eg, ammonia), disrupting normal brain activity^1,2

Precipitating factors can trigger an HE episode, including³:

and up to40%will have an overt HE episode³

Delayed recognition and management of HE may lead to worse outcomes¹¹

HE symptom assessments should be performed routinely, especially in patients with a previous episode or risk factors¹²

Check for physical signs of chronic liver disease and HE during the physical examination, such as asterixis, extrapyramidal dysfunction, hyperreflexia, and slow speech

Gathering patient history (including from caregivers) and performing a physical examination^3,12-14

Assessing mental status and sleep alterations^3,12

In one study,
caregivers were shown to have helped identify 25% of overt HE episodes¹⁴