What is the initial treatment for hepatic encephalopathy?

Initial Treatment for Hepatic Encephalopathy

Lactulose is the first-line treatment for episodic overt hepatic encephalopathy (OHE), with identification and treatment of precipitating factors being equally crucial for effective management. 1

Treatment Algorithm

Step 1: Identify and Treat Precipitating Factors

• Identifying and treating precipitating factors is paramount in HE management, as nearly 90% of patients can be treated with just correction of the precipitating factor 1
• Common precipitating factors include:
  • Gastrointestinal bleeding
  • Infection
  • Constipation
  • Excessive protein intake
  • Dehydration
  • Renal dysfunction
  • Electrolyte imbalance
  • Psychoactive medications
  • Acute hepatic injury 2

Step 2: Initiate Lactulose Therapy

• Begin lactulose at 25-45 mL orally every 1-2 hours until the patient has at least 2 bowel movements per day 1, 2
• After initial response, titrate the dose to maintain 2-3 soft bowel movements daily 2
• For patients unable to take oral medications, administer lactulose via nasogastric tube 2
• For severe HE (West-Haven criteria grade ≥3) or when oral/nasogastric administration isn't possible, use lactulose enema (300 mL lactulose in 700 mL water) 3-4 times daily until clinical improvement 2, 3

Step 3: Monitor Response and Adjust Therapy

• Careful dose adjustment is critical - overuse of lactulose can lead to complications such as aspiration, dehydration, hypernatremia, severe perianal skin irritation, and can even precipitate HE 1
• Lack of effect should prompt a search for unrecognized precipitating factors and competing causes for brain impairment 1

Alternative or Additional Agents for Non-responders

If patients do not respond adequately to lactulose and treatment of precipitating factors:

• Rifaximin (550 mg twice daily or 400 mg three times daily) can be added to lactulose for better outcomes 2, 4

  • Combination therapy with rifaximin and lactulose shows better recovery from HE (76% vs. 44%) and shorter hospital stays compared to lactulose alone 2
  • Rifaximin is particularly well-documented for maintaining remission in patients who have already experienced one or more bouts of OHE while on lactulose treatment 1

• Other alternative or additional agents for non-responders include:

  • Oral branched-chain amino acids (BCAAs) at 0.25 g/kg/day 1, 2
  • Intravenous L-ornithine L-aspartate (LOLA) at 30 g/day (note: oral LOLA is ineffective) 1, 2
  • Neomycin (4-12 g/day in divided doses) - though limited by potential for ototoxicity, nephrotoxicity, and neurotoxicity with long-term use 1, 5
  • Metronidazole - limited by neurotoxicity with prolonged use 1

Mechanism of Action

• Lactulose reduces intestinal pH through bacterial degradation to acetic and lactic acids 2, 6
• This acidification traps ammonia as non-absorbable ammonium (NH4+) in the colon, reducing plasma ammonia concentrations 3, 6
• Lactulose also increases lactobacillus count and bacterial incorporation of nitrogen, reducing the production of ammonia and other potential cerebral toxins 6

Important Clinical Considerations

• Controlling precipitating factors is the cornerstone of HE management - this alone can resolve HE in up to 90% of patients 1
• Blood ammonia levels alone do not add diagnostic, staging, or prognostic value for HE in patients with chronic liver disease - a normal value should prompt diagnostic reevaluation 1
• For patients with transjugular intrahepatic portosystemic shunt (TIPS), standard HE therapy may be less effective; shunt diameter reduction may be necessary in cases of persistent HE 1
• Secondary prophylaxis after an episode of overt HE is recommended to prevent recurrence 1