Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot

• Published in: European journal of gastroenterology & hepatology Vol. 30; no. 10; p. 1237
• Main Authors: Abdel-Razik, Ahmed, Mousa, Nasser, Shabana, Walaa, Refaey, Mohamed, Elzehery, Rasha, Elhelaly, Rania, Zalata, Khaled, Abdelsalam, Mostafa, Eldeeb, Ahmed A, Awad, Mahmoud, Elgamal, Ayman, Attia, Ahmed, El-Wakeel, Niveen, Eldars, Waleed
• Format: Journal Article
• Language: English
• Published: England 01.10.2018
• Subjects: Adult; Alanine Transaminase - blood; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Aspartate Aminotransferases - blood; Body Mass Index; Double-Blind Method; Endotoxins - blood; Female; gamma-Glutamyltransferase - blood; Humans; Insulin Resistance; Interleukin-6 - blood; Keratin-18 - blood; Male; Middle Aged; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - physiopathology; Rifaximin - adverse effects; Rifaximin - therapeutic use; Time Factors; Toll-Like Receptor 4 - blood; Tumor Necrosis Factor-alpha - blood
• ISSN: 1473-5687
• DOI: 10.1097/MEG.0000000000001232

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study. BMI, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll-like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-α, and cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6 months of rifaximin therapy (1100 mg/day). Patients were randomized into two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of rifaximin therapy, patients with NASH showed a significant reduction in homeostatic model assessment, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, endotoxin, toll-like receptor-4, IL-6, tumor necrosis factor-α, CK-18, and NAFLD-liver fat score (all P<0.05), but no changes in the lipid profile; moreover, there was a mild nonstatistically significant reduction of BMI. However, in the placebo group, there was no significant difference in these variables at baseline and after therapy. Rifaximin therapy appears to be effective and safe in modifying NASH through reduction of serum endotoxin and improvement of insulin resistance, proinflammatory cytokines, CK-18, and NAFLD-liver fat score.