Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

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

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

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.