Rifaximin Modify the Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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In this multicentric, double-blind, randomized,placebo-controlled study, the investigators hypothesized that rifaximin might act on Gram-negative bacteria and intestinal bacterial overgrowth(IBO) thereby inhibiting lipopolysaccharides(LPS)-mediated proinflammatory cytokine production. This work evaluates the efficacy of 6 months administration of rifaximin in NAFLD patients.

Detailed Description
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The investigators aimed to study the effect of rifaximin on NASH. 50 patients with biopsy-proven NASH were enrolled in this double-blind, randomized,placebo-controlled study. BMI, AST, ALT, gamma glutamyl transferase (γ-GGT), lipid profile, homeostatic model assessment (HOMA), serum endotoxin, Toll-like receptor 4 (TlR4), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α) and cytokeratin-18 (CK-18) levels were measured before and after a 6 month administration of rifaximin (1100mg/day, 550 mg tablets 1 × 2 before meals).

Official Title
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Could Rifaximin Modify the Pathogenesis of NAFLD? AMulticenter, Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Rifaximin group 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women or men aged 18-65 years. biopsy-proven NASH without or with mild to moderate fibrosis (fibrosis stage 0-3)in the preceding year. persistently abnormal ALT on 2 occasions. participants have provided written informed consent before screening. all patients counseled about the standard of care treatment (e.g., diet andexercise). Strict requirements for weight stability between the time of biopsy and study entry. Exclusion Criteria: Cirrhotic NAFLD (METAVIR stage 4). Combined viral hepatitis B and C infection. increased alcohol intake (>20 g/day) and hypothyroidism. co-existence of another type of biliary tract or pancreatic or liver diseases lactating or pregnant women. allergy to rifamycin or rifaximin. systemic inflammatory conditions (e.g. Connective tissue diseases and inflammatory bowel diseases). bariatric surgery and blind loop. evidence of hepatic decompensation (ascites, hepatic encephalopathy, and varices), history of myocardial infarction and/ or stroke within 6 months. drugs that alter the gut flora e.g. Lactulose, systemic antibiotic, cholestyramine within three months, (l) cancers especially HCC, and (m)patients with renal impairment (estimated GFR <60ml/min/1.73m2). (n) Major dose change orintiation of biguanides, metformin, thiazolidinediones, insulin, fibrates, statins, and anti-obesity medications within three months before the onset of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Rifaxmin group | Drug: Rifaximin group 1<br>* Rifaximin: 1100mg/day, 550 mg tablets 1 × 2 before meals<br>|
| 2<br>placebo group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum ALT | U/l | 6 months | 
| serum endotoxins | EU/ml | 6 months | 
| TLR-4 | ng/ml | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Glucose | mg/dl | 6 months | 
| , Insulin, | μIU/ml | 6 months | 
| CK-18,TNF-α, IL-6, IL 10 | pg/ml | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, Rifaximin, Endotoxin and Homeostatic Model Assessment