Why is rifaximin (rifamycin derivative) used in chronic liver disease?

Rifaximin in Chronic Liver Disease: Role in Hepatic Encephalopathy Management

Rifaximin is primarily used in chronic liver disease as an effective add-on therapy to lactulose for prevention of recurrent hepatic encephalopathy (HE), significantly reducing HE episodes and hospitalizations by targeting ammonia-producing gut bacteria. 1, 2

Mechanism and Efficacy

• Rifaximin is a minimally absorbed (less than 0.4%) oral antibiotic that acts locally in the gut to reduce intestinal flora, particularly ammonia-producing bacteria 2, 3
• Ammonia plays a central role in HE pathogenesis, and reducing its production is a key treatment strategy 4
• As an add-on to lactulose, rifaximin reduces the risk of HE recurrence by 58% compared to placebo (hazard ratio 0.42; 95% CI, 0.28-0.64; p<0.001) 5, 2
• Combination therapy with rifaximin and lactulose is superior to lactulose alone, with recurrence rates of 22.1% vs 45.9% 2, 5

Clinical Guidelines for Use

When to Use Rifaximin

1. First-line therapy for HE is lactulose 1, 2
2. Add rifaximin (550 mg twice daily) after the second episode of HE within 6 months 1, 2
3. Consider rifaximin monotherapy only when lactulose is poorly tolerated 2

Dosing Recommendations

• Standard dosage: 550 mg twice daily 1, 2
• Some evidence suggests once-daily dosing (550 mg daily) may be equally effective, potentially reducing costs 6
• Over 90% of patients in clinical trials received concomitant lactulose therapy 5

Benefits Beyond HE Prevention

• Reduces HE-related hospitalizations (13.6% vs 22.6% with placebo; hazard ratio 0.50; 95% CI, 0.29-0.87; p=0.01) 5
• Improves health-related quality of life compared to placebo 4
• Maintains efficacy for extended periods (up to 2.5 years) without new safety concerns 4
• Has minimal systemic adverse effects due to limited absorption 3

Safety Profile

• Adverse event rates similar to placebo in clinical trials 5, 4
• Most common adverse events (10-15% of patients): ascites, dizziness, fatigue, peripheral edema 3
• Low risk of bacterial resistance and Clostridium difficile-associated colitis even with long-term use 2
• Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 2

Clinical Considerations

• High cost may be a barrier to long-term adherence 1, 2
• Not recommended for routine prophylaxis post-TIPS (transjugular intrahepatic portosystemic shunt) 1
• Therapeutic education for patients and caregivers improves medication adherence and helps with early recognition of HE symptoms 2
• Not effective for prevention of post-TIPS HE when compared to placebo 1

Other Treatments for HE

• Lactulose remains first-line therapy for HE 1, 2
• L-ornithine L-aspartate (LOLA) may be considered for patients unresponsive to conventional therapy 1
• Oral branched-chain amino acids (BCAAs) can be used as alternative or additional agents for non-responders 1
• Neomycin and metronidazole are alternative choices but have significant long-term toxicity concerns 1
• Flumazenil, probiotics, zinc supplementation, and glycerol phenylbutyrate are not routinely recommended 1

Rifaximin represents a significant advance in HE management, particularly for preventing recurrence in patients with chronic liver disease who have already experienced episodes of HE despite lactulose therapy.