What are the stages and treatment options for Hepatic Encephalopathy (HE)?

Hepatic Encephalopathy Staging and Treatment

Staging Classification

Hepatic encephalopathy should be conceptualized as a continuum from unimpaired cognition through coma, with staging divided by severity to reflect the degree of self-sufficiency and need for care. 1

West Haven Criteria Grading System

The West Haven Criteria (WHC) is the standard clinical grading system for overt HE, supplemented by Glasgow Coma Scale (GCS) for grades III-IV 1, 2:

Covert HE (Not Clinically Obvious):

• Minimal HE: No obvious clinical signs but abnormalities on neuropsychological/neurophysiological testing 2
• Grade I: Mild alterations in consciousness, subtle personality/behavior changes, decreased attention, sleep disturbances (sleep-wake inversion), irritability or apathy, difficulty with complex cognitive tasks 3, 2

Overt HE (Clinically Apparent):

• Grade II: Mild disorientation (especially temporal), more pronounced lethargy or apathy, inappropriate behavior, asterixis, dysarthric or slow speech, evident alterations in psychometric tests 3, 2
• Grade III: Marked disorientation, somnolence to semi-stupor but responsive to verbal stimuli, marked confusion, requires ICU monitoring due to airway compromise risk 2
• Grade IV: Coma, unresponsive to verbal or noxious stimuli, requires ICU monitoring 2

Type Classification

HE is also classified by underlying etiology 2:

• Type A: Acute liver failure
• Type B: Portosystemic shunt without significant liver disease
• Type C: Cirrhosis with or without portosystemic shunt (most common)

Diagnostic Approach

The diagnosis of HE is made through exclusion of other causes of brain dysfunction, not by any single confirmatory test. 1

Clinical Diagnosis

• Overt HE (Grades II-IV): Diagnosed by clinical criteria using WHC and GCS 1
• Covert HE: Requires neuropsychological or neurophysiological testing by experienced examiners 1
• Screening tool: Animal naming test can detect covert HE 1, 3

Laboratory and Imaging

• Ammonia levels: Increased blood ammonia alone does not add diagnostic, staging, or prognostic value; however, a normal ammonia level should prompt diagnostic reevaluation for alternative causes 1, 2
• Brain imaging: CT or MRI should be performed for first-time HE to exclude other causes (especially intracerebral hemorrhage, which has 5-fold increased risk), but does not contribute to HE diagnosis or grading 1, 2

Treatment Algorithm

Four-Pronged Management Approach

All grades of HE require a systematic four-pronged approach: 1, 2

1. Initiation of care for altered consciousness
2. Identify and treat alternative causes of altered mental status
3. Identify and correct precipitating factors (resolves up to 90% of cases) 1, 3
4. Commence empirical HE treatment

Identifying and Correcting Precipitating Factors

This is the cornerstone of HE management and resolves nearly 90% of cases. 1, 3 Common precipitating factors include:

• Infections (especially spontaneous bacterial peritonitis)
• Gastrointestinal bleeding
• Constipation
• Dehydration
• Electrolyte disturbances (especially hyponatremia) 1
• Sedative medications
• Proton pump inhibitor use 1

Grade-Specific Treatment

Grades 0-I (Covert HE):

• Can be managed on medicine ward 3
• Testing and treatment should be considered for patients with impaired quality of life, employment implications, or public safety concerns (e.g., driving) 1
• A therapeutic trial with lactulose or rifaximin may strengthen diagnosis 1
• Avoid sedatives when possible 3
• Frequent mental status checks with ICU transfer if consciousness declines 3

Grade II:

• Lactulose is first-line treatment, titrated to achieve 2-3 soft stools per day 3, 2, 4
• Identify and correct precipitating factors 3
• Can typically be managed on medicine ward but monitor closely for progression 3

Grades III-IV:

• Requires ICU monitoring due to airway compromise risk 2
• Lactulose administration (oral or enema routes) 2
• Add GCS assessment for monitoring 2
• Consider rifaximin as add-on therapy 2

Pharmacologic Treatment

First-Line: Lactulose

• FDA-approved for prevention and treatment of portal-systemic encephalopathy 4
• Dose titrated to achieve 2-3 soft stools per day 3, 2
• Mechanism: Acidifies gastrointestinal tract, inhibiting ammonia production by coliform bacteria 5
• Clinical response observed in approximately 75% of patients 4

Second-Line: Rifaximin

• FDA-approved for reduction in risk of overt HE recurrence in adults 6
• In clinical trials, 91% of patients used lactulose concomitantly 6
• Dosing: 550 mg twice daily 6
• Mechanism: Decreases intestinal ammonia production and absorption by altering gastrointestinal flora 5
• Not studied in patients with MELD scores >25; only 8.6% of trial patients had MELD >19 6

Prophylaxis Strategies

After First Episode (Secondary Prophylaxis):

• Secondary prophylaxis with lactulose is recommended after the first episode of overt HE 1, 3
• Rifaximin is recommended as adjunct to lactulose after recurrent episodes 3

Primary Prophylaxis:

• Not routinely required except in high-risk patients (e.g., those with gastrointestinal bleeding) 1
• For GI bleeding: Use rifaximin or lactulose 7

Liver Transplantation

Recurrent intractable overt HE, together with liver failure, is an indication for liver transplantation evaluation 1, 2

Critical Pitfalls to Avoid

• Failing to identify and treat precipitating factors (the most common error, as this resolves 90% of cases) 1, 3, 2
• Not titrating lactulose dose adequately to achieve 2-3 stools per day 3, 2
• Relying exclusively on ammonia levels for diagnosis, staging, or monitoring 1, 2
• Not considering secondary prophylaxis after the first episode of overt HE 3, 2
• Confusing HE with other causes of altered mental status without proper workup 3, 2
• Using sedatives in patients at risk, as they worsen encephalopathy and have delayed clearance in liver failure 3