What are the treatment recommendations for hepatic encephalopathy?

Treatment Recommendations for Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, titrated to achieve 2-3 soft bowel movements per day, with rifaximin 550 mg twice daily added after recurrent episodes. 1

Immediate Management Priorities

Identify and Correct Precipitating Factors

• Systematically search for and treat precipitating factors, which resolve approximately 90% of cases. 1 Common triggers include:
  • Infections (perform thorough infectious workup) 1
  • Gastrointestinal bleeding (check for melena, hematemesis) 1
  • Constipation (assess bowel movement frequency) 1
  • Dehydration and electrolyte disturbances (check sodium, potassium, magnesium, phosphate) 1, 2
  • Sedative medications (review medication list and discontinue if possible) 1, 2
  • Acute kidney injury (monitor creatinine and urine output) 1

Determine Level of Care

• Grades 3-4 hepatic encephalopathy require ICU admission due to aspiration risk and inability to protect the airway. 1
• Grades 1-2 can be managed on a medicine ward with frequent mental status checks and transfer to ICU if consciousness declines. 1, 2

First-Line Pharmacologic Treatment

Lactulose Dosing

• Start lactulose 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements daily. 3
• For patients unable to take oral medications, administer via nasogastric tube. 3
• Clinical response occurs in approximately 75% of patients, with blood ammonia reduction of 25-50%. 4, 3
• Avoid overuse of lactulose, which can lead to aspiration, dehydration, hypernatremia, and perianal skin irritation. 3

Special Scenario: Gastrointestinal Bleeding

• For patients with GI bleeding, use rapid removal of blood from the GI tract using lactulose or mannitol by nasogastric tube, or lactulose enemas. 1

Secondary Prophylaxis After First Episode

Long-Term Lactulose

• Continue lactulose indefinitely as secondary prophylaxis after the first episode of overt hepatic encephalopathy to prevent recurrence. 1
• This recommendation is based on evidence showing lactulose prevents recurrence (19.6% recurrence with lactulose vs 46.8% with placebo). 5

Adding Rifaximin

• Add rifaximin 550 mg twice daily when a patient experiences more than one additional episode within 6 months of the first episode. 1, 6
• Rifaximin reduces the risk of hepatic encephalopathy recurrence by 58% when added to lactulose. 1, 3
• The combination improves recovery within 10 days and shortens hospital stays. 3
• In clinical trials, 91% of patients were using lactulose concomitantly with rifaximin. 6

Alternative and Add-On Therapies

When Standard Therapy Fails

• IV L-ornithine L-aspartate can be used as an alternative or additional agent for patients nonresponsive to conventional therapy (note: oral formulation is ineffective). 3
• Oral branched-chain amino acids improve manifestations and can be used as alternative or additional therapy (IV formulation is ineffective for acute episodes). 3

Nutritional Management

Protein and Feeding Strategy

• Do not restrict protein, as protein restriction worsens malnutrition and sarcopenia, which are risk factors for hepatic encephalopathy. 1
• Encourage small, frequent meals throughout the day with a late-night snack. 1, 3
• Address malnutrition present in approximately 75% of patients. 1, 2
• Provide multivitamin supplementation. 2
• Avoid fasting periods which can worsen hepatic encephalopathy. 3

Special Clinical Scenarios

Post-TIPS Patients

• Neither rifaximin nor lactulose prevents post-TIPS hepatic encephalopathy better than placebo, and routine prophylactic therapy is not recommended. 1, 3

When to Consider Transplant Evaluation

• Refer for transplant evaluation after the first episode of overt hepatic encephalopathy, or for recurrent or persistent hepatic encephalopathy not responding to treatment. 1
• Recurrent intractable hepatic encephalopathy together with liver failure is an indication for liver transplantation. 2, 3
• For patients with preserved liver function and recurrent hepatic encephalopathy, evaluate for large spontaneous portosystemic shunts that may be amenable to embolization. 3

Discontinuing Prophylaxis

• Prophylactic therapy may be discontinued only when precipitating factors are well-controlled, infections treated, variceal bleeding resolved, or liver function/nutritional status significantly improved. 2

Critical Pitfalls to Avoid

• Failing to seek precipitating factors, which cause 90% of cases. 2
• Not titrating lactulose dose adequately to achieve 2-3 stools per day. 2
• Confusing hepatic encephalopathy with other causes of altered mental status (perform brain CT to exclude other causes). 2
• Relying exclusively on ammonia levels for diagnosis—isolated blood ammonia determination does not provide diagnostic, prognostic, or staging value. 2
• Not considering secondary prophylaxis after the first episode. 2