Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Primary endpoint: Bacterial infections after 90 days. Secondary endpoints: : 2.1. Liver function tests 2.2. Levels of endotoxemia 2.3. Complications of liver cirrhosis. 2.4. Survival

Official Title
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Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: Prednisone
* Drug: Rifaximin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisone<br>Prednisone PO 40mg/day for 30 days plus standard supportive care measurements | Drug: Prednisone<br>* Prednisone PO 40mg/day or IV equivalent dosage for 30 days. Patients not responding at 7 days (e.g. Lille Model ≥ 0.45) treatment with Prednisone will be suspended.<br>|
| Experimental: Prednisone plus Rifaximin<br>Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements | Drug: Prednisone<br>* Prednisone PO 40mg/day or IV equivalent dosage for 30 days. Patients not responding at 7 days (e.g. Lille Model ≥ 0.45) treatment with Prednisone will be suspended.<br>Drug: Rifaximin<br>* Rifaximin PO 1200 mg/day for 90 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of bacterial infections | Development of any bacterial infection. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Decompensations of Liver Cirrhosis | Development of any liver cirrhosis decompensations Hepatic Encephalopathy Acute Kidney Injury (including Hepatorenal Syndrome) Acute variceal bleeding Ascites Death | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic Hepatitis, Bacterial Infections, Acute-on-Chronic Liver Failure