When is lactulose (lactulose) versus rifaximin (rifaximin) used in the treatment of Hepatic Encephalopathy (HE)?

Lactulose vs. Rifaximin in Hepatic Encephalopathy Management

Lactulose should be used as first-line therapy for initial episodes of overt hepatic encephalopathy (OHE), while rifaximin should be added to lactulose after a second episode of OHE recurrence for prevention of further episodes. 1, 2

Initial Treatment of Overt Hepatic Encephalopathy

• Lactulose is the first-choice treatment for episodic OHE due to its effectiveness and low cost 1
• Initial lactulose dosing: 25-30 mL (20-30g) every 1-2 hours orally until the patient has at least 2 bowel movements per day 1
• For maintenance, titrate lactulose to achieve 2-3 soft stools daily 1
• For severe HE (West-Haven criteria grade 3 or more) or patients unable to take oral medications, lactulose can be administered via enema (300 mL lactulose and 700 mL water) 3-4 times daily 1

When to Add Rifaximin

• Add rifaximin to lactulose therapy after a second episode of OHE recurrence 1, 2
• Rifaximin dosage for HE: 550 mg orally twice daily 1, 3
• Rifaximin plus lactulose combination has shown better recovery from HE (76% vs. 44%, p=0.004) and shorter hospital stays (5.8 vs. 8.2 days, p=0.001) compared to lactulose alone 1, 4
• In the clinical trials for rifaximin in HE, 91% of patients were using lactulose concomitantly 3

Special Considerations

• Rifaximin should not be used as monotherapy for HE; it should be added to lactulose 2
• Rifaximin may be limited in cases of severe HE (grade 3 or more) due to the need for oral administration 1
• Lactulose overuse can lead to complications including aspiration, dehydration, hypernatremia, and severe perianal skin irritation 2
• Always identify and treat precipitating factors of HE (gastrointestinal bleeding, infection, constipation, excessive protein intake, dehydration, renal dysfunction, electrolyte imbalance, psychoactive medications, acute hepatic injury) 1

Alternative Therapies for Non-Responders

• For patients not responding to conventional therapy, consider:
  • Oral branched-chain amino acids (BCAAs) 1, 2
  • Intravenous L-ornithine L-aspartate (LOLA) 1
• Neomycin and metronidazole are alternative choices but not recommended for long-term use due to side effects (ototoxicity, nephrotoxicity, peripheral neuropathy) 1

Long-term Management

• Continue lactulose for prevention of recurrent episodes of HE 1, 5
• Long-term rifaximin plus lactulose significantly reduces the risk of OHE recurrence and HE-related hospitalization compared with lactulose alone 5
• Rifaximin has not been studied in patients with MELD scores >25, and only 8.6% of patients in controlled trials had MELD scores over 19 3

Common Pitfalls to Avoid

• Not identifying and treating precipitating factors of HE 1
• Using rifaximin alone without lactulose 2
• Excessive lactulose dosing leading to complications 2
• Not considering rifaximin add-on therapy after multiple recurrences despite lactulose treatment 1, 2
• Long-term use of neomycin or metronidazole due to toxicity risks 1