Alcoholic Hepatitis
Conditions
Keywords
Alcoholic Hepatitis, Bacterial Infections, Acute-on-Chronic Liver Failure
Brief 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.
Detailed description
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
Interventions
DRUGPrednisone
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.
DRUGRifaximin
Rifaximin PO 1200 mg/day for 90 days
Sponsors
Germans Trias i Pujol Hospital
Hospital del Mar
Hospital de Sant Pau
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of bacterial infections | 90 days | Development of any bacterial infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decompensations of Liver Cirrhosis | 90 days | Development of any liver cirrhosis decompensations 1. Hepatic Encephalopathy 2. Acute Kidney Injury (including Hepatorenal Syndrome) 3. Acute variceal bleeding 4. Ascites 5. Death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Endotoxemia serum levels | 90 days | Measurement of serum changes in endotoxemia levels during the rifaximin treatment. |
Countries
Spain
Outcome results
None listed