Effect of Probiotics on Gut-Liver Axis of Alcoholic Hepatitis

Study Overview
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Brief Summary
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Background/Aims: The investigators explored the therapeutic effects of probiotics in patients with AH. Methods: Between December 2012 and January 2015, the investigators conducted a 7-day, double-controlled, randomized, prospective clinical trial comparing the efficacy of probiotics in improving liver enzymes, LPS, pro-inflammatory cytokines, stool culture, and stool Polymerase chain reaction denaturing gradient gel electrophoresis. AH was defined as an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 and elevated AST (ALT) level with an alcohol consumption history within 48 hours. Patients were randomized to receive 7 days of cultured Lactobacillus rhamnosus R0011/acidophilus R0052 (120 mg/day) or placebo. The levels of liver enzymes, modified Discriminant Function (mDF), LPS, and pro-inflammatory cytokines, stool culture, and stool Polymerase chain reaction denaturing gradient gel electrophoresis were checked at baseline and again after therapy.

Detailed Description
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Background/Aims: Alcoholic hepatitis (AH) is one of the leading causes of liver diseases. Gut-derived microbial lipopolysaccharide (LPS) has been known as a central role in the pathogenesis of AH. Some animal studies suggested an emerging role of probiotics in restoration of the bowel flora and improving liver enzymes. We explored the therapeutic effects of probiotics in patients with AH. Methods: Between December 2012 and January 2015, the investigators conducted a 7-day, double-controlled, randomized, prospective clinical trial comparing the efficacy of probiotics in improving liver enzymes, LPS, pro-inflammatory cytokines, stool culture, and stool Polymerase chain reaction denaturing gradient gel electrophoresis. AH was defined as an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 and elevated AST (ALT) level with an alcohol consumption history within 48 hours. Patients were randomized to receive 7 days of cultured Lactobacillus rhamnosus R0011/acidophilus R0052 (120 mg/day) or placebo. The levels of liver enzymes, modified Discriminant Function (mDF), LPS, and pro-inflammatory cytokines, stool culture, and stool Polymerase chain reaction denaturing gradient gel electrophoresis were checked at baseline and again after therapy.

Official Title
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Effect of Probiotics on Gut-Liver Axis of Alcoholic Hepatitis

Conditions
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Alcoholic Liver Disease

Intervention / Treatment
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* Drug: Probiotics (Lacidofil®)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcoholic hepatitis (AST/ALT >2 & elevated AST (ALT) level Alcohol >60 g/day (M), >40 g/day (F) during 7 days before screening Last drinks: within 48 hours prior to admission) Exclusion Criteria: viral hepatitis, autoimmune hepatitis, pancreatitis, hemochromatosis, Wilson's disease, Drug-Induced Liver Injury, cancer, infection need for antibiotics, severe AH, or obesity (BMI >30 kg/m2)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>For Probiotics, 7 days | Drug: Placebo<br>* For probiotics<br>* Other names: For probiotics;|
| Active Comparator: Probiotics<br>Probiotics of 120 mg/day for 7days | Drug: Probiotics (Lacidofil®)<br>* 7 days of cultured Lactobacillus rhamnosus R0011/acidophilus R0052 (120 mg/day)<br>* Other names: Lacidofil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liver enzymes |  | 7 days after probiotics | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPS and pro-inflammatory cytokines |  | 7 days after probiotics | 
| Stool culture and stool Polymerase chain reaction denaturing gradient gel electrophoresis |  | 7 days after probiotics | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis, Probiotics, Lipopolysaccharides, Cytokines, Alcoholics