Rifamycin in Minimal Hepatic Encephalopathy

Inclusion Criteria: 1. Age 18-75 years 2. Cirrhosis defined by any one of the following 1. Cirrhosis on liver biopsy or transient elastography 2. Nodular liver on imaging 3. Endoscopic or radiological evidence of varices in a patient with chronic liver disease 4. Platelet count \<150,000/mm3 and AST/ALT ratio \>1 in a patient with chronic liver disease 3. Women of childbearing age will need to be on accepted birth control for 10 days prior to entering study and 30 days after the end of the last dose of the study drug. 4. Cognitive impairment on PHES aggregate score \[more than or greater than\] -4SD or EncephalApp Stroop - based on norms published in Allampati et al located at the website www.encephalapp.com17 (This is the accepted diagnosis of minimal HE.) 5. Willing and able to participate, provide samples and complete follow-up 6. Stable Liver function tests between 2-12 weeks prior to enrollment (can include the screening laboratory values details in exclusion criteria) Exclusion Criteria: 1. Unclear diagnosis of cirrhosis (does not meet the criteria outlined above) 2. Child score \>8 3. Increasing trend of ALT and AST in the 2-12 weeks prior to study inclusion (Baseline values established by at least two samples obtained at least 2 weeks and no more than 8-12 weeks apart) to account for disease related changes in liver enzymes and bilirubin while on study that may otherwise be inappropriately attributed to study drug. \>20% increase in baseline serum AST, ALT, ALP and total bilirubin (TBL) will be considered an exclusion criterion. 4. Unable to consent, follow for the study duration 5. Normal performance on PHES 6. Mini-mental status exam\<2518 7. Recent alcohol abuse (within 3 months) 8. Recent illicit drug abuse (within 3 months) except marijuana 9. Current use of psychoactive drugs apart from long-standing opioids or stable anti-depressant use. 10. Prior overt HE episodes defined as West-Haven Criteria grade 2 or higher in the past that required hospitalization or initiation of lactulose or rifaximin therapy 11. Currently on lactulose or rifaximin 12. Current or recent invasive bacterial or fungal infections (\<1 month) 13. Allergic reactions to rifamycin, rifampin or rifaximin 14. MELD \>20 15. TIPS placement 16. Serum sodium\<125 17. On SBP prophylaxis 18. Post-transplant cirrhosis 19. Infections within 4 weeks 20. End-stage organ failures: CHF with EF\<25%, End-stage renal disease on dialysis, COPD on home oxygen 21. Pregnancy (positive urine pregnancy test at screening) 22. In the opinion of the PI, those who are unlikely to survive or remain without liver transplant for 6 weeks, or cannot adhere to the trial activities.