Why is rifaximin used for hepatic encephalopathy?

October 14, 2025 •

3 min read

Up to 40% of patients with cirrhosis experience hepatic encephalopathy (HE), a condition that significantly impacts survival. A key treatment strategy involves asking, why is rifaximin used for hepatic encephalopathy? This antibiotic targets the gut to reduce toxin buildup.

Quick Summary

Rifaximin is a minimally absorbed antibiotic used to manage hepatic encephalopathy by altering gut bacteria to reduce ammonia production. This lowers blood ammonia levels, preventing recurrent HE episodes and related hospitalizations.

Key Points

Core Function: Rifaximin is used for hepatic encephalopathy (HE) because it is a minimally absorbed antibiotic that reduces ammonia-producing bacteria in the gut.
Ammonia Reduction: High ammonia levels are a key cause of HE's neuropsychiatric symptoms; rifaximin lowers these levels by altering the gut microbiome.
Recurrence Prevention: Clinical trials show rifaximin significantly reduces the risk of recurrent overt HE episodes by 58% and hospitalizations by 50%.
Combination Therapy: It is often used as an add-on to lactulose, with the combination being more effective than lactulose alone for preventing HE recurrence and reducing mortality.
Mechanism of Action: Rifaximin works by inhibiting bacterial RNA synthesis, which halts the growth of targeted gut bacteria.
Safety Profile: The medication is generally well-tolerated with a low rate of side effects, making it suitable for long-term use in chronic liver disease patients.
Targeted Action: Because it is not significantly absorbed into the bloodstream, rifaximin acts almost exclusively in the gut, minimizing systemic side effects.

Understanding Hepatic Encephalopathy (HE)

Hepatic encephalopathy (HE) is a serious complication of advanced liver disease, such as cirrhosis. It causes neuropsychiatric issues from mild cognitive changes to coma. These symptoms occur because the damaged liver can't filter toxins, primarily ammonia, which is produced by gut bacteria. Ammonia travels to the brain, causing swelling and impaired function. HE is linked to frequent hospitalizations and increased mortality.

The Gut-Liver-Brain Axis and Ammonia's Role

HE is connected to the gut-liver-brain axis. In cirrhosis, changes in gut bacteria lead to excess ammonia production. Increased gut permeability allows ammonia and other toxins to enter the bloodstream. A healthy liver would filter these, but a cirrhotic liver cannot, allowing toxins to reach the brain and cause HE symptoms. Reducing blood ammonia is a main treatment goal.

Why is rifaximin used for hepatic encephalopathy? The Core Mechanism

Rifaximin is an oral antibiotic that is minimally absorbed, working mainly in the gut. This allows it to target the source of ammonia production in HE.

Rifaximin inhibits bacterial RNA synthesis, reducing ammonia-producing bacteria in the gut and thus decreasing absorbed ammonia. By changing gut bacteria and lowering ammonia, it helps prevent HE neurological symptoms. Rifaximin also has anti-inflammatory effects and may improve the gut barrier, further reducing toxin translocation.

Clinical Efficacy and Recurrence Prevention

Studies show rifaximin is effective for HE. One key trial found rifaximin, often with lactulose, reduced the risk of recurrent overt HE episodes by 58% and HE-related hospitalizations by 50% over six months compared to placebo. This makes rifaximin a core therapy for preventing recurrence after a previous HE episode. For every four patients treated for six months, one overt HE episode is prevented. Long-term studies confirm its safety and efficacy for recurrence prevention.

Rifaximin vs. Other HE Treatments

Lactulose is a first-line HE therapy. It acidifies the colon, trapping ammonia, and acts as a laxative. Rifaximin is often used with lactulose for inadequate response or recurrence prevention.

Comparison Table: Rifaximin vs. Lactulose


Feature	Rifaximin	Lactulose
Mechanism	Reduces ammonia-producing gut bacteria by inhibiting bacterial RNA synthesis.	Lowers colon pH to trap ammonia; acts as a laxative to increase bowel movements.
Primary Use	Prevention of recurrent overt HE episodes, often as an add-on to lactulose.	First-line treatment for acute HE and prevention of recurrence.
Efficacy	Significantly reduces HE recurrence and hospitalizations, especially when combined with lactulose.	Effective in reversing HE, but rifaximin monotherapy may be more effective for reducing recurrence.
Common Side Effects	Generally well-tolerated; may include nausea, dizziness, fatigue, and abdominal pain.	Can cause significant diarrhea, bloating, gas, and electrolyte imbalances.
Adherence	Better tolerated, which may lead to better patient adherence.	Side effects like diarrhea and unpleasant taste can make long-term adherence difficult.

Combination therapy with rifaximin and lactulose is superior to lactulose alone in reducing HE recurrence, hospitalizations, and mortality.

Dosage, Side Effects, and Long-Term Safety

Rifaximin is generally well-tolerated long-term. Common side effects are usually mild and can include nausea, dizziness, fatigue, headaches, abdominal pain, and muscle spasms.

The risk of Clostridioides difficile infection seems low, though reported. Long-term studies show a safety profile similar to placebo and fewer GI side effects than lactulose.

Conclusion

Rifaximin is crucial for long-term HE management because it targets toxin production in the gut. By reducing ammonia-producing bacteria with minimal systemic effects, it significantly lowers the risk of HE recurrences and hospitalizations. Its better tolerability than lactulose and proven efficacy, especially with lactulose, make it valuable for improving quality of life and prognosis for chronic liver disease patients.

For more information, consult authoritative sources such as the American Association for the Study of Liver Diseases (AASLD): https://www.aasld.org/

Frequently Asked Questions

Rifaximin is an antibiotic that works inside the gut to reduce the number of ammonia-producing bacteria. By lowering ammonia production, it helps prevent this toxin from reaching the brain and causing the neurological symptoms of hepatic encephalopathy.

Yes, rifaximin is very often prescribed along with lactulose. Studies have shown that the combination of rifaximin and lactulose is more effective at preventing recurrent hepatic encephalopathy and related hospitalizations than lactulose alone.

Rifaximin is generally well-tolerated. Some common side effects may include nausea, dizziness, fatigue, abdominal pain, headaches, and muscle cramps. Its side effect profile is often more favorable than lactulose's.

For preventing recurrence of hepatic encephalopathy, rifaximin is often used as a long-term or maintenance therapy. Studies have evaluated its safety and effectiveness for periods extending beyond two years. The exact duration should be determined by a healthcare provider.

Clinical studies have shown that rifaximin reduces the risk of a breakthrough hepatic encephalopathy episode by 58% compared to placebo over a 6-month period. It also reduces the risk of HE-related hospitalization by 50%.

Rifaximin can be expensive, but it is covered by most Medicare Part D plans and other health insurance providers for the treatment of hepatic encephalopathy. Despite its cost, studies suggest it can be cost-effective by reducing hospitalizations.

Rifaximin is an oral medication and is typically taken by mouth.