Inclusion Criteria:  Participant has a diagnosis of advanced liver cirrhosis with medically controlled ascites (>30 days) not requiring therapeutic paracentesis (prophylactic variceal banding allowed if no history of previous variceal bleeding). Participant has a Child-Pugh B Classification (score of 7 to 9 inclusive) without OHE and a Model End-Stage Liver Disease Sodium (MELD-Na) score of <15 at Visit 1. Participant has a Conn (West Haven Criteria) score of <2 without known neurologic, psychiatric or iatrogenically induced increase. Participant has a Mini-Mental State Examination (MMSE) score ≥ 24 and demonstrates no cognitive impairment upon exam at screening and baseline. Participant is at least 18 and ≤70 years of age. Females of childbearing (reproductive) potential must have a negative serum or urine pregnancy test at screening. All participants must agree to use 2 acceptable methods of contraception throughout their participation in the study. Participant must be able to independently read, fully understand and provide written informed consent on the Institutional Review Board (IRB)/Ethics Committee (EC) approved informed consent form (ICF) without additional support and provide authorization as appropriate per local privacy regulations.  Exclusion Criteria:  Participant has an active coronavirus disease 2019 (COVID 19) infection that is unresolved or, in the opinion of the investigator, may affect evaluation of the study drug or place the subject at undue risk Participant has a history of anaphylaxis or hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of rifaximin. Participant has a history of drug-induced liver injury, drug rash with eosinophilia and systemic symptom (DRESS) syndrome. Participant has a history or current clinical suspicion of hepatopulmonary syndrome. Participant has a history of SBP, primary or secondary SBP prophylaxis, EVB, or AKI-HRS. Participant has a documented history of an OHE episode (Conn score ≥ 2) or has a history of rifaximin 550 mg and lactulose use for suspected OHE episode. Participant has either: a) no history of ascites -or- b) uncontrolled ascites. Participant has other non-controllable neurological or psychiatric conditions which may confound the assessment of cognitive function (e.g., dementia, schizophrenia, etc.). Participants with focal neurological deficits due to a neurological event such as cerebrovascular accident. Participants with Wernicke's or Wernicke-Korsakoff encephalopathy. Participant has signs of alcohol use disorder, defined as Alcohol Use Disorders Identification Test (AUDIT-10) score of >7, within 6 months of signing the ICF. Participant has pseudomembranous colitis, abdominal abscess, or clinically significant strictures and fistulas of the gastrointestinal tract. Participant has epilepsy and experienced a seizure within 12 weeks prior to screening. Participant consumes more than moderate amounts of alcohol, defined as 1 standard drink per day for women and 2 standard drinks per day for men. Participant has a history of substance abuse < 6 months prior to signing the ICF and cannot refrain from substance abuse during the study period. Participant is currently taking narcotics, benzodiazepines, or psychoactive medicines which cannot be discontinued. Participant is currently taking an anticoagulant Participant has been diagnosed with an uncontrolled infection < 4 weeks prior to screening. Participant has been diagnosed with an upper gastrointestinal bleed from non-variceal sources < 6 weeks prior to screening. Participant shows the presence of intestinal obstruction or has inflammatory bowel disease. Participant has undergone bariatric surgery or intestinal resection. Participant has a history of portal vein thrombosis, a history of a transjugular intrahepatic portosystemic shunt (TIPS) procedure, or plans to undergo a TIPS procedure. Participant has a history of shunt surgery or direct intrahepatic portocaval shunt (DIPS) procedure for portal hypertension or plans to undergo a DIPS procedure. Participant has a history of peritoneal dialysis. Participant has undergone prophylactic variceal banding within 2 weeks of screening or is scheduled to undergo prophylactic variceal banding during the study (Note: participants with previous prophylactic variceal banding will be allowed to participate in the study). Participant has Type 1 or Type 2 diabetes that is not adequately controlled in the opinion of the investigator. Participant has severe co-morbid disease with a life expectancy < 1 year. Participant has active malignancy (except basal carcinoma of the skin), including active hepatocellular carcinoma (HCC) and/or a past history of HCC. Participants with resections or ablations of squamous cell carcinoma of the skin, or in situ carcinoma of the cervix, that occurred greater than 6 months prior to screening and are considered disease free are eligible for enrollment. Evidence of HCC or a lesion suspicious for HCC within 6 months on ultrasound or contrast multiphase magnetic resonance imaging (MRI) or computed tomography (CT). If this imaging is not available, or if alpha-fetoprotein (AFP) ≥ 20 ng/ml at screening, participants should undergo standard of care diagnostic procedures with their personal physician to rule out HCC during the screening period. Participant requires hemodialysis. Participant has any condition or circumstance that adversely affects the participant, could cause noncompliance with treatment or visits, may impact the interpretation of clinical data, could cause bias, or may otherwise contraindicate the participant's participation in the study. Participant used any investigational product or device within 30 days or 5 half-lives of the investigational product (whichever comes first) of providing consent.