Introduction

Hepatic encephalopathy (HE) presents as a spectrum of neuropsychiatric abnormalities ranging from minimal cognitive changes to profound coma. In the critical care setting, early recognition of subtle neurologic deficits, exclusion of common mimics, and standardized severity grading using systems like the West Haven Criteria are essential to optimize patient outcomes and guide appropriate therapeutic interventions.

1. Clinical Assessment

A focused neurologic examination—evaluating consciousness, attention, and motor signs—remains the cornerstone of HE diagnosis. The findings are often dynamic and can fluctuate throughout the day.

Mental Status & Attention

• Orientation: Assess orientation to person, place, and time. Note any fluctuating levels of arousal or lethargy.
• Attention Tasks: Simple bedside tasks can reveal subtle deficits. Common examples include serial subtractions (e.g., counting down from 100 by 7s), reciting the months of the year in reverse, or the clock-drawing test.
• Minimal HE: In patients with suspected minimal HE, the bedside exam may appear normal. Formal psychometric testing should be considered if there is a high index of suspicion.

Neuromotor Signs

• Asterixis: This “flapping tremor” is a classic sign. Ask the patient to extend their arms, dorsiflex their wrists, and hold the position. Observe for irregular, brief, and jerky lapses in posture.
• Other Signs: In more advanced HE, hyperreflexia, increased muscle tone, and extrapyramidal features such as rigidity or bradykinesia may be present.

2. Laboratory Evaluation

Laboratory studies are crucial for identifying and correcting precipitants of HE and ruling out other metabolic causes of altered mental status. However, they must be interpreted with caution.

Serum Ammonia

While historically linked to HE, serum ammonia levels have limited diagnostic utility. There is a poor correlation between the ammonia level and the clinical severity of HE, and a normal level does not rule out the diagnosis. Its measurement is plagued by preanalytical issues, including prolonged tourniquet time, delayed sample processing, and the patient’s acid–base status, all of which can alter the result.

Core Laboratory Panels

• Liver & Coagulation: Bilirubin, transaminases, and albumin reflect the degree of underlying hepatic dysfunction. The INR and platelet count are vital for assessing bleeding risk, especially before invasive procedures.
• Renal & Electrolytes: Azotemia (from dehydration or hepatorenal syndrome) and electrolyte disturbances (especially hyponatremia and hypokalemia) are common and potent precipitants of HE.
• Exclusionary Tests: Always check a blood glucose to rule out hypoglycemia. Blood cultures, urinalysis, and inflammatory markers are essential to identify infection. When indicated, toxicology screens can rule out sedative or other drug effects.

3. Neurophysiological and Imaging Modalities

EEG and neuroimaging are not used to diagnose HE but are valuable supportive tools to exclude other serious conditions that can mimic its presentation.

Electroencephalogram (EEG)

The EEG in HE typically shows a progressive, generalized slowing of brain wave activity, with a shift from normal alpha waves to theta and delta waves. In severe cases, characteristic “triphasic waves” may be seen. The primary role of EEG is to differentiate HE from nonconvulsive status epilepticus, which can present similarly with altered mental status but requires urgent antiepileptic treatment.

CT/MRI of the Brain

Neuroimaging is not routinely required for every episode of HE, especially in patients with a known history. However, it is strongly indicated in specific situations:

• A first-time presentation of HE to rule out chronic structural lesions.
• Any history of recent head trauma.
• The presence of new focal neurologic deficits (e.g., unilateral weakness).

In these cases, imaging helps exclude intracranial hemorrhage, ischemic stroke, or mass lesions.

4. Classification Systems

Standardized grading of HE severity is crucial for clear communication among clinicians, directing the appropriate level of care, and determining the intensity of therapy.

West Haven Criteria (Grades 0–4)

The West Haven Criteria (WHC) is the most widely used system for grading overt HE in the clinical setting. It provides a simple, clinically based framework for staging severity.

ISHEN Consensus and Minimal HE

The International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) provides further guidance:

• Overt HE: Defined as West Haven Grade 2 or higher.
• Covert HE: A term encompassing West Haven Grade 1 and Minimal HE.
• Minimal HE (MHE): Diagnosed when the clinical exam is normal (Grade 0) but deficits are detected on specialized testing. ISHEN recommends using at least two validated psychometric or neurophysiological tests, such as the Psychometric Hepatic Encephalopathy Score (PHES), Inhibitory Control Test (ICT), or Critical Flicker Frequency (CFF). Screening for MHE is important in high-risk patients (e.g., MELD score >15) as its detection and treatment can reduce the risk of falls and improve quality of life.

5. Differential Diagnosis and Exclusion of Mimics

Hepatic encephalopathy is fundamentally a diagnosis of exclusion. It is imperative to systematically rule out other common causes of altered mental status in a patient with liver disease before attributing the findings solely to HE.

• Sepsis-Associated Encephalopathy: Can be difficult to distinguish from HE. Look for signs of systemic inflammation like fever, hemodynamic instability, and elevated inflammatory markers.
• Wernicke’s Encephalopathy: A neurologic emergency caused by thiamine deficiency. The classic triad is ophthalmoplegia, ataxia, and confusion. Maintain a high index of suspicion in malnourished patients.
• Other Metabolic/Toxic Causes: Always consider hypoglycemia, uremia, hypercapnia, and intoxication from sedatives, narcotics, or alcohol.

6. Integration into Management Pathways

The primary goals of management are to ensure patient safety, identify and correct precipitating factors, and initiate ammonia-lowering therapy. The clinical grade of HE directly guides the intensity and setting of care.

Risk Stratification and Treatment Setting

• Grades 1–2 (Covert/Mild Overt HE): These patients can often be managed on a medical ward. Treatment focuses on oral lactulose (with or without rifaximin) and frequent serial neurologic exams to monitor for improvement or deterioration.
• Grades 3–4 (Severe Overt HE): These patients require admission to an intensive care unit (ICU). The primary concern is airway protection due to the high risk of aspiration. Management involves more intensive intravenous therapies and continuous monitoring.

Key Management Principles