What is the treatment for hepatic encephalopathy?

Treatment of Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, with rifaximin added for patients with recurrent episodes or inadequate response to lactulose alone. 1, 2, 3

Immediate Management Priorities

Airway Protection and Stabilization

• Intubate immediately if the patient has grade III-IV encephalopathy (West Haven criteria), as these patients cannot protect their airway and are at high risk for aspiration. 4
• Elevate the head of bed to 30 degrees to reduce intracranial pressure. 4
• Provide intensive care monitoring for higher grades of HE. 1

Identify and Treat Precipitating Factors

This step is critical—identifying and correcting precipitating factors alone can treat nearly 90% of patients. 1, 4

Common precipitating factors and their management: 5, 4

• Gastrointestinal bleeding: Perform endoscopy, complete blood count, digital rectal examination, stool blood test; treat with transfusion, endoscopic therapy, or vasoactive drugs. 5, 4
• Infection: Check 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. 5, 4
• Constipation: Evaluate with history-taking and abdominal X-ray; treat with enema or laxatives. 5
• Dehydration/renal dysfunction: Assess skin elasticity, blood pressure, pulse rate, serum creatinine, electrolytes; stop or reduce diuretics and provide fluid therapy (intravenous albumin infusion). 5
• Electrolyte disturbances (hyponatremia, hypokalemia): Check serum electrolytes; stop or reduce diuretics, restrict fluids for hyponatremia. 5
• Benzodiazepines or opioids: Obtain medication history; discontinue offending agents, consider flumazenil for benzodiazepines or naloxone for opioids. 5

First-Line Pharmacological Treatment

Lactulose Dosing

Start lactulose immediately at 30-45 mL (20-30 g) every 1-2 hours orally or via nasogastric tube until the patient has at least 2 bowel movements. 4

• Initial phase: Administer 25-30 mL every 1-2 hours until rapid laxation is achieved. 1, 4
• Maintenance phase: Titrate to achieve 2-3 soft bowel movements per day. 5, 1, 2
• Lactulose reduces blood ammonia levels by 25-50% and achieves clinical response in approximately 75% of patients. 2
• The mechanism involves acidification of intestinal pH through production of acetic and lactic acids, conversion of ammonia to less absorbable ammonium, and osmotic laxative effect that flushes ammonia out. 5

Critical pitfall: Overuse of lactulose can paradoxically precipitate HE through excessive diarrhea leading to dehydration and electrolyte disturbances. 1

Second-Line and Add-On Therapies

Rifaximin

Add rifaximin 550 mg orally twice daily for patients with recurrent HE or inadequate response to lactulose alone. 1, 3

• Rifaximin is FDA-approved for reduction in risk of overt HE recurrence in adults. 3
• In clinical trials, 91% of patients were using lactulose concomitantly with rifaximin. 3
• Rifaximin decreases intestinal production and absorption of ammonia by altering gastrointestinal flora and is almost completely excreted unchanged in feces. 6
• It has fewer side effects compared to neomycin or metronidazole. 7

Alternative Antibiotics

• Neomycin and metronidazole are alternative choices for overt HE, but long-term use is limited by ototoxicity, nephrotoxicity, and neurotoxicity. 1
• These should only be considered when rifaximin is unavailable or not tolerated. 8

Additional Therapeutic Options

• Oral Branched-Chain Amino Acids (BCAAs): Can be used as an alternative or additional agent for patients not responding to conventional therapy; meta-analyses show improvement in manifestations of episodic HE. 1
• IV L-Ornithine L-Aspartate (LOLA): Alternative for patients not responding to conventional therapy; improves psychometric testing and reduces postprandial venous ammonia levels. 1

Prevention of Recurrence

Secondary prophylaxis after an episode of overt HE is strongly recommended. 1

• Best-documented regimen: Lactulose plus rifaximin for maintaining remission. 1
• Continue maintenance therapy at hospital dismissal to prevent further episodes. 8
• Provide careful instructions to patients and caregivers about dose titration to achieve 3 bowel movements daily. 8
• Primary prophylaxis is not required except in patients with cirrhosis at high risk for developing HE. 1

Special Considerations

Nutritional Management

Do not restrict protein intake in cirrhotic patients with hepatic encephalopathy, as it increases protein catabolism. 4

• Patients with mild HE can be fed orally as long as cough and swallow reflexes are intact. 4

Management of Agitation

• Use haloperidol 0.5-5 mg PO/IM every 8-12 hours for mild to moderate agitation. 4
• Avoid benzodiazepines as they have delayed clearance in liver failure and worsen encephalopathy. 4

Post-TIPS HE

• Neither rifaximin nor lactulose has been shown to prevent post-TIPS HE better than placebo. 1
• Shunt diameter reduction may be necessary if severe HE occurs after TIPS. 1

Liver Transplantation

• Recurrent intractable overt HE, together with liver failure, is an indication for liver transplantation. 1
• For patients with preserved liver function, evaluate for large spontaneous portosystemic shunts. 1

Monitoring

Critical Parameters

• Perform frequent neurological evaluations for signs of intracranial hypertension. 4
• Monitor hemodynamic parameters, renal function, glucose, and electrolytes. 4

Ammonia Levels

Venous blood ammonia levels are not proportional to the degree of HE and are not associated with prognosis. 5, 4

• However, if patients with suspected HE show normal ammonia concentrations, differentiation from other diseases is required. 5

Common Pitfalls to Avoid

• Failure to identify precipitating factors may lead to poor treatment response. 1
• Delaying treatment while awaiting diagnostic confirmation can worsen outcomes. 1
• Protein restriction is counterproductive and should be avoided. 4
• Using benzodiazepines for agitation will worsen encephalopathy due to delayed clearance in liver failure. 4