What are the stages and treatment options for hepatic encephalopathy?

Hepatic Encephalopathy Grading and Treatment

Grading System

Hepatic encephalopathy should be graded using the West Haven Criteria (WHC) for overt HE, with the Glasgow Coma Scale added for grades III-IV, while covert HE (minimal HE and grade I) requires neuropsychological or neurophysiological testing for diagnosis. 1, 2

West Haven Criteria Grades

• Grade 0 (Minimal HE): No obvious clinical signs but abnormalities detected on neuropsychological/neurophysiological tests such as PHES, CRT, ICT, SCAN, Stroop, CFF, or EEG 1, 2

• Grade I (Covert HE): Mild alterations in consciousness, subtle personality changes, decreased attention, sleep disturbances, irritability or apathy, difficulty with complex cognitive tasks 3, 2

• Grade II: Mild disorientation, pronounced lethargy, inappropriate behavior, asterixis, dysarthric or slow speech 3

• Grade III: Marked disorientation, somnolence to semi-stupor but responsive to verbal stimuli, severe confusion 3, 2

• Grade IV: Coma, unresponsive to verbal or noxious stimuli 3, 2

Clinical Classification by Type

• Type A: Acute liver failure 2
• Type B: Portosystemic shunt without significant liver disease 2
• Type C: Cirrhosis with or without portosystemic shunt 2

Treatment Approach

Four-Pronged Management Strategy

All patients with overt HE require immediate treatment using a four-pronged approach: stabilization of altered consciousness, exclusion of alternative causes, identification and correction of precipitating factors, and empirical HE treatment with lactulose. 1, 3, 2

1. Stabilization Based on Grade

Grades I-II:

• Manage on medicine ward with frequent mental status checks, though ICU is preferable 3
• Transfer to ICU immediately if consciousness declines 3
• Avoid sedatives as they worsen encephalopathy and have delayed clearance in liver failure 3

Grades III-IV:

• Require ICU admission with intensive monitoring 3, 2
• Intubate the trachea to protect airway 3
• Elevate head of bed 3
• Minimize stimulation 3
• Cerebral edema occurs in 25-35% of grade III patients and 65-75% of grade IV patients 3

2. Exclude Alternative Causes

• Obtain brain imaging (CT or MRI) to rule out other causes, particularly for first-time presentations, as intracranial hemorrhage risk is increased 5-fold in cirrhotic patients 1, 4
• Blood ammonia levels do not add diagnostic, staging, or prognostic value; however, a normal ammonia level should prompt reconsideration of the diagnosis 1, 4

3. Identify and Correct Precipitating Factors

This is the cornerstone of management—correcting precipitating factors resolves HE in nearly 90% of patients. 1, 3, 4

Common precipitating factors include:

• Gastrointestinal bleeding 4
• Infection 4
• Constipation 4
• Dehydration 4
• Hyponatremia 4
• Hypokalemia 4

4. Empirical Pharmacologic Treatment

First-Line: Lactulose

• Start lactulose 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements daily 3, 5
• Achieves clinical response in approximately 75% of patients 3, 5
• Can be administered via nasogastric tube in patients unable to swallow or at aspiration risk 1
• Reduces blood ammonia levels by 25-50% 5

Second-Line: Rifaximin

• Add rifaximin 550 mg twice daily if patient has recurrent episodes despite lactulose 3, 6
• Reduces HE recurrence risk by 58% when added to lactulose 3
• In clinical trials for HE, 91% of patients were using lactulose concomitantly 6

Prophylaxis Strategies

Secondary Prophylaxis (Mandatory):

• Secondary prophylaxis with lactulose is mandatory after the first episode of overt HE 1, 3, 4
• Continue lactulose indefinitely, titrated to 2-3 soft stools daily 3
• Add rifaximin 550 mg twice daily after the second episode or if recurrence occurs despite lactulose 3, 4

Primary Prophylaxis:

• Not required except in patients with cirrhosis at known high risk to develop HE 1, 2

Covert HE (Minimal HE and Grade I)

• Testing should be considered in patients with impaired quality of life, employment implications, or public safety concerns (e.g., driving skills, work performance) 1, 2
• Treatment is not routinely recommended but may be considered in specific circumstances affecting daily functioning 1, 2

Nutritional Management

Do not restrict protein—this worsens malnutrition and sarcopenia, which are risk factors for HE. 3

• Provide moderate hyperalimentation with small, frequent meals throughout the day 3, 4
• Include a late-night snack 3, 4
• Avoid fasting periods which worsen HE 3

Liver Transplantation

• Evaluate for liver transplantation after the first episode of overt HE 3
• Recurrent intractable overt HE with liver failure is an indication for liver transplantation 1, 2, 4

Critical Pitfalls to Avoid

• Failing to systematically search for precipitating factors, which cause 90% of cases 3, 2
• Not titrating lactulose adequately to achieve 2-3 stools per day 3, 2
• Confusing HE with other causes of altered mental status 3, 2
• Not initiating secondary prophylaxis after the first episode 3, 2
• Relying exclusively on ammonia levels for diagnosis—they lack diagnostic, staging, or prognostic value 1, 3
• Restricting protein intake, which worsens outcomes 3