What is the initial management for patients with Non-Alcoholic Steatohepatitis (NASH) who develop hepatic encephalopathy?

Initial Management of Hepatic Encephalopathy in NASH Patients

The first-line treatment for hepatic encephalopathy in patients with NASH is lactulose administration at a dose of 25 mL orally every 12 hours, adjusted to achieve 2-3 soft stools per day, along with identification and correction of precipitating factors. 1

Diagnosis and Assessment

• Overt hepatic encephalopathy (OHE) is diagnosed by clinical criteria and graded according to the West Haven Criteria:

  • Grade I: Minimal changes in behavior, minimal changes in consciousness
  • Grade II: Gross disorientation, drowsiness, inappropriate behavior, asterixis
  • Grade III: Marked confusion, incoherent speech, sleeping most of time but arousable
  • Grade IV: Comatose, unresponsive to pain, decerebrate posturing 1

• Rule out other causes of altered mental status through appropriate testing 2

• Normal ammonia levels question the diagnosis of hepatic encephalopathy and require reevaluation 1

Four-Pronged Treatment Approach

1. Initiate appropriate care for altered consciousness

   • Patients with higher grades of HE who cannot protect their airway need intensive care monitoring 2, 1

2. Identify and treat alternative causes of altered mental status

   • Brain imaging studies should be considered in cases of diagnostic doubt 1

3. Identify and correct precipitating factors

   • Approximately 90% of patients can be treated solely by correcting precipitating factors 2, 1
   • Common precipitating factors include:
     • Gastrointestinal bleeding
     • Infection/sepsis
     • Constipation
     • Electrolyte disturbances
     • Dehydration
     • Medication non-compliance
     • Excessive protein intake
     • Use of sedatives or tranquilizers 1

4. Commence empirical HE treatment

Specific Pharmacological Management

First-Line Treatment

• Lactulose: 25 mL orally every 12 hours, adjusted to achieve 2-3 soft stools per day 1
  • For patients unable to take oral medications, lactulose enemas (300 mL in 700 mL water) can be used 1, 3
  • Lactulose works by acidifying the gastrointestinal tract, which inhibits ammonia production by coliform bacteria 4

Second-Line/Adjunctive Treatment

• Rifaximin: 550 mg twice daily should be added to lactulose after a second episode of hepatic encephalopathy within 6 months 1, 5
  • Rifaximin decreases intestinal production and absorption of ammonia by altering gut flora 4
  • FDA-approved for reducing the risk of overt HE recurrence 5
  • Has been shown to reduce HE-related hospitalizations by 50% 5

Nutritional Management

• Avoid protein restriction
  • Recommended protein intake is 1.2-1.5 g/kg/day 1
  • Provide small, frequent meals throughout the day and a snack before bedtime 1

Monitoring and Follow-up

• Regular assessment of mental status to monitor response to treatment 1
• Monitor blood sodium levels to maintain >130 mmol/L, ideally >135 mmol/L 1
• Limit proton pump inhibitors to strict validated indications 1
• Avoid benzodiazepines in patients with decompensated cirrhosis 1

Long-term Management

• Secondary prophylaxis after an episode of overt HE is strongly recommended 2, 1
• Primary prophylaxis is not required except in patients with cirrhosis at high risk for developing HE 2, 1
• The first episode of overt hepatic encephalopathy should prompt referral to a transplant center for evaluation 1
• Recurrent intractable OHE, together with liver failure, is an indication for liver transplantation 2, 1

Common Pitfalls to Avoid

1. Failing to identify and treat precipitating factors (can resolve HE in up to 90% of cases) 1
2. Restricting protein intake unnecessarily, which can worsen nutritional status 1
3. Not considering rifaximin as adjunctive therapy for recurrent episodes 5, 4
4. Overlooking the need for liver transplant evaluation after the first episode of overt HE 1
5. Ignoring the impact of minimal hepatic encephalopathy on quality of life, driving skills, and work performance 2, 1