RICE Trial: Rifaximin In Chronic Hepatic Encephalopathy - A Randomized, Controlled Trial

Inclusion Criteria: 1. Cirrhosis of any cause 2. History of previous admission for acute HE within 12 months of screening and Conn grade 0-1 HE at time of enrollment 3. An Institutional Review Board (IRB/EC) approved informed consent is signed and dated prior to any study-related activities being initiated. 4. Subject is a male or a non-pregnant and non-lactating female. Women of non-childbearing potential or who are practicing adequate birth control are eligible. The investigator is responsible for determining whether the subject has adequate birth control for study participation. 5. Subject is ≥18 years of age. 6. Subject is capable and willing to comply with all study procedures. 7. If the subject has a history of a portal-systemic shunt, shunt placement or revision must be \>6 months from Screening for TIPS or a surgical shunt. Exclusion Criteria: 1. Subject has a significant medical or psychiatric condition which, in the opinion of the Investigator, precludes participation in the study. 2. Subject has a history of allergy or intolerance to lactulose. 3. Subject has a history of allergy or intolerance to rifampin or rifaximin. 4. Subject has participated in an investigational drug or device study within the 30 days prior to study screening. 5. Subject is pregnant or is lactating. 6. Subject shows evidence of ongoing alcohol or drug dependence, in the opinion of the Investigator. 7. Subject has a visual impairment disorder (e.g., glaucoma, diabetic retinopathy, or macular degeneration) or a neurological disease beyond HE that, in the opinion of the Investigator, could impact their performance on neuropsychological assessments and psychometric tests. 8. Subject has any condition or circumstance that would, in the opinion of the Investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments or visits. 9. Subject's current, required medications are on prohibited concurrent medication listing. 10. Hemoglobin \< 8.0 at time of screening 11. Severe hypovolemia or electrolyte abnormalities that would be likely to affect mental function (serum sodium less than 120 mEq/L, serum calcium greater than 11 mg/dL) at time of screening 12. Ongoing gastrointestinal bleeding at time of screening 13. Chronic renal insufficiency with a serum creatinine \> 3.0 at time of screening 14. History of tuberculosis infection