What is the best course of treatment for a patient with suspected hepatic encephalopathy and a history of liver disease, presenting with signs of hepatic encephalopathy?

Treatment of Hepatic Encephalopathy in Chronic Liver Disease

Start lactulose immediately at 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements per day, and aggressively identify and treat precipitating factors—this approach resolves 75-90% of cases. 1, 2, 3

Immediate Diagnostic Workup

Before initiating treatment, measure plasma ammonia—a normal level brings the diagnosis of hepatic encephalopathy into serious question and mandates evaluation for alternative causes of altered mental status. 1

Identify precipitating factors immediately, as correcting these alone resolves approximately 90% of cases: 3

• Gastrointestinal bleeding: Check complete blood count, perform digital rectal examination, and proceed with urgent endoscopy if melena or hematemesis present 1, 3
• Infection: Obtain blood cultures, urinalysis with culture, chest X-ray, and diagnostic paracentesis if ascites present to rule out spontaneous bacterial peritonitis 1, 3
• Constipation: Document bowel movement frequency 1, 3
• Electrolyte disturbances: Check basic metabolic panel for hypokalemia, hyponatremia, and renal dysfunction 3
• Medications: Review for benzodiazepines, opioids, and diuretics 1

Perform brain imaging (CT or MRI) if diagnostic uncertainty exists, focal neurological deficits are present, or the patient fails to respond to treatment within 24-48 hours—though no imaging modality proves hepatic encephalopathy, imaging excludes structural lesions like intracranial hemorrhage. 1

ICU Admission Criteria

Transfer patients with West Haven grade 3-4 hepatic encephalopathy to the ICU immediately, as they cannot protect their airway and risk aspiration. 1, 3 Intubation is indicated when Glasgow Coma Score falls below 7-8. 3

First-Line Pharmacological Treatment

Lactulose is the cornerstone of treatment and should never be delayed: 1, 2, 3, 4

• Dosing: Start 25-45 mL (20-30 g) orally or via nasogastric tube every 1-2 hours until bowel movements occur, then adjust to 25 mL twice daily 2, 3, 4
• Target: 2-3 soft bowel movements per day 1, 2
• Efficacy: Reduces blood ammonia by 25-50% and achieves clinical response in approximately 75% of patients 2, 4
• Mechanism: Reduces ammonia production and absorption in the gut 4

For patients with gastrointestinal bleeding, rapid removal of blood from the GI tract using lactulose or mannitol by nasogastric tube (or lactulose enemas) prevents hepatic encephalopathy development. 1

Adding Rifaximin

Add rifaximin 550 mg twice daily if the patient experiences more than one additional episode of overt hepatic encephalopathy within 6 months of the first episode, or if lactulose alone fails to improve symptoms within 24 hours. 1, 2, 3

The combination of lactulose plus rifaximin reduces:

• Hepatic encephalopathy recurrence from 53% to 34% 2
• 30-day readmissions 2
• Mortality by 40% 2

Secondary Prophylaxis After First Episode

After the first episode of overt hepatic encephalopathy resolves, continue lactulose indefinitely as secondary prophylaxis, titrated to 2-3 soft stools per day. 1, 2, 3 This is a strong recommendation based on Level 1 evidence. 1

Add rifaximin 550 mg twice daily permanently after a second episode within 6 months. 1, 2

Critical Management Pitfalls

Never restrict protein in hepatic encephalopathy patients—this worsens sarcopenia and paradoxically increases hepatic encephalopathy risk. 1, 3 Instead, provide 1.2-1.5 g/kg/day protein and 35-40 kcal/kg/day energy intake with small frequent meals (4-6 times daily including nighttime snack). 2

Do not routinely correct coagulopathy with fresh frozen plasma or vitamin K unless active bleeding or invasive procedures are planned, as this does not improve outcomes and increases volume overload risk. 3

Liver Transplantation Evaluation

Refer to a transplant center immediately after the first episode of overt hepatic encephalopathy for evaluation. 1, 2, 3 Patients with recurrent or persistent hepatic encephalopathy despite optimal medical therapy are transplant candidates, as hepatic encephalopathy is potentially fully reversible post-transplant. 3

One-year survival after first hepatic encephalopathy episode is only 42%, declining to 23% at 3 years, making early transplant evaluation critical. 2

Patient and Caregiver Education

Provide structured education covering: 1, 2, 3

• Medication effects and side effects (diarrhea from lactulose is expected and therapeutic)
• Critical importance of adherence—missing doses precipitates recurrence
• Early warning signs: confusion, sleep-wake reversal, asterixis
• Actions to take: increase lactulose for mild symptoms, seek emergency care if fever or severe confusion develops

Structured 15-minute education sessions reduce hepatic encephalopathy-related hospitalization by 86%. 2

Patients with hepatic encephalopathy cannot drive—this must be explicitly communicated. 3

Follow-Up Monitoring

Schedule close outpatient follow-up to: 1

• Confirm neurological status has returned to baseline
• Adjust lactulose dose to maintain 2-3 soft stools daily
• Screen for covert hepatic encephalopathy using the Animal Naming Test
• Assess gait, fall risk, and functional status
• Prevent precipitating factors (constipation, infection, medication errors)