effects of rifaximin in patients with acute alcoholic hepatitis

Conditions: Alcoholic Hepatitis

Summary: acute alcoholic hepatitis (aah) is a serious condition and one of the most frequent causes of acute-on-chronic liver failure. the current standard therapy (corticosteroids) is theme of debate and unsatisfactory in many patients (year mortality: 30%). one of the main causes of death is bacterial infections, which affect 40-50% of patients at 90 days. intestinal decontamination with rifaximin (a nonabsorbable antibiotic) reduces endotoxemia, improves liver function and reduces the complications of decompensated alcoholic cirrhosis. the hypothesis/objective: to assess whether oral decontamination with rifaximin prevents the development of infections associated with aah and analyze its consequences.

design: open multicenter comparative study. a cohort (n = 66) will receive rifaximin (1200 mg / d) for 90 days. results will be compared with those of a cohort of aah prospectively included in an observational study. both groups with a uniform treatment protocol (which includes the administration of corticosteroids and standardized treatment for complications of liver failure). patients will be monitorized until hospital discharge and a follow-up visit at 7, 30, 45, 60 and 90 days will be performed. endpoints: 1. primary endpoint: bacterial infections after 90 days. 2. secondary endpoints: : 2.1. liver function tests 2.2. levels of endotoxemia 2.3. complications of liver cirrhosis. 2.4. survival

Eligibility criteria:
inclusion criteria: * patients ≥18 and \<70 years of age. * active alcohol abuse and excessive alcohol consumption prior to admission defined as \> 50 g per day for men and\> 40 g per day for women. * jaundice (bilirubin \>2 mg/dl) for no more than 3 months. * clinical suspicion of alcoholic hepatitis with a modified maddrey's discriminant function \> 32 points. exclusion criteria: * hypersensitivity to rifaximin * advanced chronic or terminal illness. advanced chronic illness will be defined as: all conditions evolved into a clinical stage to limit the patient's functional status (eg, heart failure nyha\> ii, copd pco2\> 50 mmhg or po2 \<60 mmhg, stroke or other disabling neurological disease, disabling or uncontrolled oncological conditions, etc ...). terminal illness will be defined as any clinical conditions with a survival expectancy less than 3 months * hepatocellular carcinoma (previously diagnosed) beyond milan's criteria. * complete portal vein thrombosis (previously diagnosed). * autoimmune liver disease. * hepatitis b and c and hiv infection (anti-hcv, surface hbv antigen and anti-hiv positive). * pregnancy or nursing. * use of rifaximin during the previous 2 months. * treatment with pentoxifylline. * lack of informed consent. removal criteria: * lack of histological confirmation of alcoholic hepatitis during the first 7 days after inclusion. because there are no non-diagnostic tools to diagnose alcoholic hepatitis, histological confirmation is required in all patients (preferably through a transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histologic features: hepatocellular damage (eg, hepatocyte ballooning and presence of mallory-denk bodies). inflammatory infiltrate (predominantly polymorphonuclear cells). pericellular or sinusoidal fibrosis. * hepatocellular carcinoma beyond milan's criteria diagnosed during the first 7 days after inclusion. * complete portal vein thrombosis diagnosed during the first 7 days after inclusion. * protocol violation. * severe adverse event directly related with rifaximin.

Keywords: alcoholic hepatitis bacterial infections acute-on-chronic liver failure