What is the treatment for hepatic (liver) encephalopathy?

Treatment for Hepatic Encephalopathy

Start lactulose immediately at 30-45 mL every 1-2 hours until the patient has at least 2 bowel movements, then titrate to 2-3 soft stools daily, while simultaneously identifying and correcting precipitating factors—this resolves symptoms in approximately 90% of cases. 1, 2

Immediate Stabilization

Airway Protection and ICU Criteria

• Intubate immediately for grade III-IV encephalopathy (marked confusion/stupor or coma) to protect the airway from aspiration 2
• Admit grade I-II patients to a medicine ward with frequent mental status checks, but transfer to ICU immediately if consciousness declines 1
• Elevate the head of bed to 30 degrees to reduce intracranial pressure 2
• Avoid sedatives entirely—they worsen encephalopathy and have delayed clearance in liver failure 1, 2

Rule Out Alternative Diagnoses

• Obtain brain imaging (CT or MRI) to exclude intracranial hemorrhage, particularly for first presentations, as cirrhotic patients have increased bleeding risk 3
• A normal ammonia level should prompt reconsideration of the diagnosis, though ammonia levels do not add diagnostic, staging, or prognostic value otherwise 3

Identify and Correct Precipitating Factors

This is the cornerstone of management—precipitating factors are present in 80-90% of cases and their correction resolves HE in nearly 90% of patients. 1, 3, 2

Systematic Search for Common Precipitants

• Gastrointestinal bleeding: Check complete blood count, perform digital rectal exam, stool blood test, and endoscopy; treat with transfusion, endoscopic therapy, or vasoactive drugs 2
• Infection: Obtain complete blood count with differential, C-reactive protein, chest X-ray, urinalysis with culture, blood culture, and diagnostic paracentesis if ascites present; treat with antibiotics 2
• Constipation, dehydration, hyponatremia, hypokalemia: Correct these metabolic derangements 3

First-Line Pharmacologic Treatment

Lactulose Dosing

• Initial phase: Administer 30-45 mL (20-30 g) every 1-2 hours orally or via nasogastric tube until rapid laxation occurs 2
• Maintenance phase: Titrate to produce 2-3 soft stools daily 1, 3, 2
• Achieves clinical response in approximately 75% of patients 1, 4
• The FDA label confirms lactulose reduces blood ammonia by 25-50%, paralleled by improvement in mental state and EEG patterns 4

Common Pitfall to Avoid

Not titrating lactulose adequately to achieve 2-3 stools per day is a critical error that leads to treatment failure. 1

Add-On Therapy for Recurrent Episodes

Rifaximin

• Add rifaximin 550 mg twice daily if the patient has recurrent episodes despite lactulose 1, 3, 5
• Reduces HE recurrence risk by 58% when added to lactulose 1
• The FDA approved rifaximin specifically for reduction in risk of overt HE recurrence in adults, with 91% of trial patients using lactulose concomitantly 5

Secondary Prophylaxis (Mandatory After First Episode)

Secondary prophylaxis with lactulose is mandatory after the first episode of overt HE and must be continued indefinitely. 1, 3

• Continue lactulose indefinitely, titrated to 2-3 soft stools daily 1
• Add rifaximin 550 mg twice daily after the second episode or if recurrence occurs despite lactulose 1, 3

Nutritional Management

Critical Dietary Principles

• Do not restrict protein—this worsens malnutrition and sarcopenia, which are risk factors for HE 1, 3, 2
• Provide moderate hyperalimentation with small, frequent meals throughout the day 1, 3
• Include a late-night snack 1, 3
• Avoid fasting periods which worsen HE 1

Management of Agitation

• Use haloperidol 0.5-5 mg PO/IM every 8-12 hours for mild to moderate agitation 2
• Avoid benzodiazepines as they have delayed clearance in liver failure and worsen encephalopathy 2

Alternative or Additional Agents

For Patients Nonresponsive to Conventional Therapy

• Oral branched-chain amino acids (BCAAs) can be used as an alternative or additional agent 6
• IV L-ornithine L-aspartate (LOLA) can be used as an alternative or additional agent 6
• Neomycin and metronidazole are alternative choices, though long-term use carries ototoxicity, nephrotoxicity, and neurotoxicity risks 6

Liver Transplantation Evaluation

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

Critical Pitfalls Summary

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