We wish to perform a multicenter, double-blind RCT with two parallel-group stratified on the center, comparing rifaximin to no rifaximin (placebo) for the primary prophylaxis of SBP in 'severe' cirrhotic patients with large ascites. The primary outcome will be the 12-month survival.

Inclusion Criteria:

• Cirrhosis diagnosed on clinical, radiological and/or histological findings

• Patients with large ascites (i.e., grade 3 ascites requiring paracentesis). Patients with grade 2 ascites are also authorized.

• Ascites with a low protein level in ascitic fluid (< 15 g/L) with one of the following three conditions:

  1. impaired renal function defined by serum creatinine ≥ 106 mmol/L, uremia ≥ 9 mmol/L or serum sodium ≤ 130 mmol/L), or
  2. severe liver impairment defined by Child-Pugh score ≥ 9 with serum total bilirubin levels ≥ 51 mmol/L.
  3. severe liver impairment defined by Child-Pugh C

• Patient who signed an informed consent form

• Patient with a social security system

• Woman must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the study if childbearing potential.

• Patients who needs a TIPS if the procedure is performed 3 months or more following the randomization

• Patients with severe alcoholic hepatitis can be considered for inclusion if the MELD score < 30 and the Maddrey Discriminant Function < 60 providing that the patient is not infected (and consequently, will not receive antibiotics) and has not yet received corticosteroid (if necessary). Patients not responding to corticosteroid at day 7 (according to the Lille score) could be include after a wash-out of steroids for a period of 7 days.

Exclusion Criteria:

• Pregnant woman or breastfeeding
• Vulnerable person regarding french law
• Individual under legal protection measure
• Individual unable to exprim his/her consent
• Person under 18 years of age and over 80 years of age
• Transplanted patients, HIV infection (or patients who deny HIV serology) or immunosuppressive therapy (including patients under corticosteroids for severe alcoholic hepatitis if the patients respond to steroids with improvement of liver function)
• Patients with a liver transplant project and an estimated waiting time for liver transplantation of 3 months or less
• Past SBP or any present bacterial infection
• Patient who have received a TIPS procedure before rhe randomization
• Patients with an alfapump
• Patient receiving antibiotics (including rifaximin) in the 7 days preceding the inclusion in this study exept for patients participating to the microbiota study (15 days).
• Hypersensitivity to rifaximin, derivatives of rifamycin or one of the constituents of the preparation
• Hepatocellular carcinoma outside the Milan criteria, other cancer at a palliative stage
• Any clinical situation with a very low short-terme prognosis (other than cirrhosis), i.e. a survival estimated lower than one month
• Gastrointestinal bleeding within 7 days
• Intestinal obstruction
• Grade 3 hepatic encephalopathy (HE) during the previous 6 months before randomization
• Chronic heart failure (stage III or IV of the New York Heart Association [NYHA] Functional Classification
• Patient judged as noncompliant
• Patients who cannot receive a clear information and who have no trusted relatives
• Patient who refuses the participation agreement by signing the information form and consent as defined in the protocol.
• Exclusion period from another biomedical study