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

Eur J Gastroenterol Hepatol. 2018 Oct;30(10):1237-1246. doi: 10.1097/MEG.0000000000001232.

Abstract

Background/aims: 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.

Patients and methods: 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).

Results: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • 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
  • 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
  • gamma-Glutamyltransferase / blood

Substances

  • Anti-Bacterial Agents
  • Endotoxins
  • IL6 protein, human
  • Interleukin-6
  • Keratin-18
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Rifaximin