What is the best approach to manage a patient with hepatic encephalopathy, likely due to cirrhosis, and a history of liver disease?

Management of Hepatic Encephalopathy

Non-absorbable disaccharides (lactulose or lactitol) are the first-line treatment for acute overt hepatic encephalopathy, with rifaximin added for recurrent episodes or when lactulose alone is insufficient. 1, 2

Immediate Assessment and Stabilization

Identify and treat precipitating factors first—this alone resolves HE in 80-90% of cases. 1

The most common precipitating factors requiring immediate attention include:

• Gastrointestinal bleeding: Check complete blood count, perform digital rectal examination, and endoscopy if indicated 1
• Infection: Obtain blood cultures, urinalysis with culture, chest X-ray, and diagnostic paracentesis if ascites present; start empiric antibiotics 1
• Constipation: Perform abdominal X-ray and initiate enema or laxatives 1
• Dehydration/electrolyte imbalance: Check serum electrolytes, particularly sodium and potassium; reduce or stop diuretics and consider albumin infusion 1
• Medications: Discontinue benzodiazepines (contraindicated in decompensated cirrhosis), opioids, and restrict proton pump inhibitors to validated indications only 1, 3

For severe HE (West Haven Grade III-IV), intubate for airway protection and transfer to intensive care unit. 1, 4, 5

Pharmacological Treatment for Acute Overt HE

First-Line: Lactulose

Administer lactulose 30-45 mL (20-30 g) orally every 1-2 hours until the patient has at least 2 bowel movements per day. 1, 2

• Lactulose reduces blood ammonia by 25-50% and achieves clinical response in approximately 75% of patients 2, 6
• After initial response, titrate dose to achieve 2-3 soft stools daily 1, 3
• If oral intake is impossible, administer via nasogastric tube 1

For severe HE (Grade ≥3) or when oral/NG administration is not feasible, perform lactulose enema: 300 mL lactulose mixed with 700 mL water, 3-4 times daily, retained for at least 30 minutes. 1

Second-Line: Add Rifaximin

Add rifaximin 550 mg twice daily when the patient does not improve with lactulose alone within 24 hours. 1, 7

• Rifaximin combined with lactulose shows superior efficacy compared to lactulose alone 1
• The combination reduces hospital-days more effectively than either agent alone (IRR 0.28) 8
• Do not use rifaximin as monotherapy for acute overt HE—always combine with lactulose initially 5

Additional Therapies (Adjunctive)

Consider intravenous L-ornithine L-aspartate (LOLA) or albumin as adjunctive therapy in severe cases. 1

• Oral branched-chain amino acids (BCAA) can be added but are not first-line 1
• Flumazenil may temporarily improve consciousness in benzodiazepine-induced HE but does not improve survival and is not recommended as routine therapy 1

Prevention of Recurrence (Secondary Prophylaxis)

After the first episode of overt HE, start indefinite secondary prophylaxis with lactulose 25 mL twice daily, titrated to 2-3 soft stools per day. 1, 3, 4

• 50-70% of patients experience recurrence within 1 year without prophylaxis 1
• After a second episode, add rifaximin 550 mg twice daily to lactulose for long-term prevention 1, 3, 7

The combination of lactulose plus rifaximin is associated with:

• 40% reduction in mortality (adjusted HR 0.40) 8
• Fewer 30-day readmissions (IRR 0.18) 8
• Reduced HE recurrence from 53% to 34% 1

Nutritional Management

Provide adequate protein intake of 1.2-1.5 g/kg/day and energy intake of 35-40 kcal/kg/day. 1, 3

• Never restrict protein long-term—this worsens sarcopenia and paradoxically increases HE risk 1, 4
• Implement small frequent meals (4-6 times daily including a nighttime snack) 1
• Weight loss and sarcopenia worsen HE outcomes and must be prevented 1, 3

Patient and Caregiver Education

Provide structured 15-minute education session covering: 1, 3

• Medication effects and side effects (diarrhea from lactulose is expected and therapeutic)
• Critical importance of adherence—non-adherence is a major precipitating factor
• Early warning signs of recurrent HE (confusion, sleep disturbance, personality changes)
• Actions to take: increase lactulose for mild symptoms, seek immediate care for fever or worsening confusion

Structured education reduces HE-related hospitalization by 86% (HR 0.14) 1

Screening and Monitoring

All patients with cirrhosis should be systematically screened for both overt and covert HE using the animal naming test (60-second bedside tool). 3

• Monitor neurological status, gait, and fall risk at each follow-up visit 1, 3
• Treatment endpoints must include both cognitive performance improvement and maintenance of daily life autonomy 1, 3

Special Considerations

Gastroenterology Consultation

Refer all patients with HE to gastroenterology—specialist involvement reduces mortality by 27% (adjusted HR 0.73) and decreases 30-day readmissions. 8

Portosystemic Shunt Occlusion

In patients with recurrent HE despite optimal medical therapy and MELD score <11, consider embolization of large spontaneous portosystemic shunts (>8 mm). 1

• Approximately 60% remain HE-free at 100 days and 50% at 2 years post-embolization 1
• This is only appropriate for stable patients with good liver function 1

Liver Transplantation

Evaluate for liver transplantation in patients with: 1, 4

• Recurrent overt HE despite optimal medical therapy
• Severe HE unresponsive to treatment
• Overall 1-year survival after first HE episode is only 42%, declining to 23% at 3 years 1

Critical Pitfalls to Avoid

• Do not assume all altered mental status is HE—obtain brain imaging to exclude structural lesions, particularly in patients with focal deficits or coagulopathy 1, 5
• Do not measure ammonia levels to guide treatment—levels do not correlate with HE severity or prognosis, though normal ammonia should prompt evaluation for alternative diagnoses 1
• Do not discharge patients without secondary prophylaxis—recurrence risk is unacceptably high without maintenance therapy 3, 5
• Do not delay treatment of precipitating factors—controlling infection, bleeding, or other triggers is paramount and HE will not fully resolve until these are addressed 1, 5
• Do not use benzodiazepines in decompensated cirrhosis—they are absolutely contraindicated 3