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
• Perform frequent neurological evaluations for signs of intracranial hypertension. 4

Identify and Treat Precipitating Factors

This step is critical—identifying and correcting precipitating factors alone can improve hepatic encephalopathy in 80-90% of patients. 5, 1, 4

Common precipitating factors and their management:

• Gastrointestinal bleeding: Evaluate with endoscopy, complete blood count, digital rectal examination, and 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, and electrolytes; stop or reduce diuretics and provide fluid therapy with intravenous albumin infusion. 5
• Medications: Stop benzodiazepines (consider flumazenil) and opioids (consider naloxone). 5

First-Line Pharmacological Treatment

Lactulose Dosing

For acute/overt hepatic encephalopathy:

• Start lactulose 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
• Maintenance dosing: Titrate to achieve 2-3 soft bowel movements per day, typically 25 mL every 12 hours. 1
• Lactulose reduces blood ammonia levels by 25-50% and achieves clinical response in approximately 75% of patients. 2

Mechanism: Lactulose is metabolized by intestinal bacteria, producing acetic and lactic acids that lower intestinal pH, convert ammonia to less absorbable ammonium, increase lactobacillus counts (which don't produce ammonia), and provide osmotic laxative effects. 5, 6

Second-Line and Add-On Therapies

Rifaximin

Rifaximin 550 mg orally twice daily is the most effective add-on therapy for prevention of recurrence and should be added to lactulose for patients with recurrent hepatic encephalopathy. 1, 3

• In clinical trials for hepatic encephalopathy, 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. 7
• Rifaximin has fewer side effects than neomycin or metronidazole. 8

Alternative Therapies for Non-Responders

For patients not responding to lactulose and rifaximin:

• Oral Branched-Chain Amino Acids (BCAAs): Can be used as an alternative or additional agent, with meta-analyses showing improvement in manifestations of episodic hepatic encephalopathy. 1
• IV L-Ornithine L-Aspartate (LOLA): Improves psychometric testing and reduces postprandial venous ammonia levels. 1
• Neomycin or metronidazole: Alternative antibiotics for overt hepatic encephalopathy, but long-term use is limited by ototoxicity, nephrotoxicity, and neurotoxicity. 1, 8

Prevention of Recurrence

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

• Best-documented regimen: Lactulose plus rifaximin for maintaining remission. 1
• Patients with recurrent hepatic encephalopathy despite lactulose benefit from adding rifaximin, which decreases frequency of recurrent episodes and related hospitalizations. 9
• Primary prophylaxis is not required except in patients with cirrhosis at high risk for developing hepatic encephalopathy. 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 hepatic encephalopathy can be fed orally as long as cough and swallow reflexes are intact. 4

Agitation Management

• 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

Seizure Management

• Phenytoin is the primary anticonvulsant for controlling seizures in hepatic encephalopathy. 10
• If benzodiazepines are absolutely necessary for uncontrolled seizures, use only minimal doses due to delayed clearance by the failing liver. 10

Post-TIPS Hepatic Encephalopathy

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

Liver Transplantation

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

Monitoring

• Venous blood ammonia levels are not proportional to the degree of hepatic encephalopathy and are not associated with prognosis, though normal ammonia in suspected hepatic encephalopathy should prompt evaluation for other causes. 5, 4
• Monitor hemodynamic parameters, renal function, glucose, and electrolytes. 4
• Regularly assess for medication side effects, particularly with long-term antibiotic use. 1

Critical Pitfalls to Avoid

• Overuse of lactulose can paradoxically precipitate hepatic encephalopathy through excessive diarrhea causing dehydration and electrolyte disturbances. 1
• Failure to identify precipitating factors leads to poor treatment response. 1
• Delaying treatment while awaiting diagnostic confirmation worsens outcomes. 1
• Patients and families should be counseled about the risk of motor vehicle accidents, which require mandatory reporting to the Department of Motor Vehicles in some states. 9