Additional Study Information: The Red-C 3131 Study is a phase 3 study is looking to see if a study medicine, rifaximin, can safely delay or prevent HE in adults who have been diagnosed with advanced liver cirrhosis. Adults who have been diagnosed with advanced liver cirrhosis, but who don't yet have HE may be eligible to join. About 466 patients will be enrolled across 200 sites. The study is a double-blind study, which means neither the participant nor the study team will know which treatment the participant is receiving. The participants will be randomly assigned to two treatment groups: the study medicine or placebo (which contains no active ingredients). During this study, the participant will attend up to 21 study visits, including 14 visits to the clinic and 7 telephone check-ins, with study participation expected to last 80 weeks (about 1.5 years). The participant will undergo clinical assessments during the study visits, such as a physical exam and vital signs. Participants will be asked questions about their medical history, have an electrocardiogram (ECG), and complete questionnaires. In addition, their blood and urine samples will be collected. Participants will also have the option of participating in a Pharmacokinetic (PK) sub-study, Optional Bacterial Resistance Sub-study, and an Optional Future Research Study. Female participants who can get pregnant will undergo pregnancy testing at every visit. To take part in this study, the pregnancy test must be negative. If the female participant gets pregnant while participating in the study, the participant will be withdrawn from the research study, and the pregnancy will be followed to observe and record its outcome. Note: Participants who develop hepatic encephalopathy during participation in the study will be treated and followed for the remainder of the study.