Simvastatin Plus Rifaximin in Decompensated Cirrhosis

Exclusion Criteria

• •Patients on treatment with statins or rifaximin one month before study inclusion.
• •Patients on the waiting list for liver transplantation.
• •Patients with acute-on-chronic liver failure according to the criteria published by Moreau et al.
• •Serum creatinine ≥2 mg/dL.
• •Serum bilirubin\>5 mg/dL.
• •INR ≥2.5.
• •Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion.
• •Bacterial infection within 15 days before study inclusion.
• •Gastrointestinal bleeding within 15 days before study inclusion.
• •Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy.
• •HIV infection.
• •Hepatocellular carcinoma outside Milan criteria, defined as a single nodule ≤5 cm or a maximum of 3 nodules with none \>3 cm.
• •Patients on antiviral therapy for HCV or those who have received it within the last 6 months.
• •Patients with previous history of myopathy.
• •Patients on treatment with potent inhibitors of CYP3A4 enzyme (See section 5.2: Concomitant, nonpermitted and permitted medication)
• •Patients on treatment with drugs with potential interactions with simvastatin
• •Patients with a history of significant extrahepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD \>2, chronic kidney disease with serum creatinine \>2mg/dL or under renal replacement therapy.
• •Patients with current extrahepatic malignancies including solid tumours and hematologic disorders.
• •Patients with previous history or increased risk of intestinal obstruction.
• •Pregnancy or breastfeeding.
• •Patients included in other clinical trials in the previous month.
• •Patients with active alcohol consumption of more than 3 units per day.
• •Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
• •Severe alcoholic hepatitis requiring corticosteroid therapy (Maddrey's Discriminant function ≥ 32 and/or ABIC score \> 6.7).
• •Refusal to give informed consent.
• •Patients with contraindications for statins or rifaximin.
• •Known hypersensitivity to rifaxamin (or rifamycin derivatives) or to simvastatin.