Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease

Abstract

Objective: Recent studies have suggested that endotoxin-induced cytokines play an important role in nonalcoholic fatty liver disease (NAFLD). Rifaximin is a nonabsorbable antibiotic that might act on Gram-negative bacteria, thereby inhibiting endotoxin proinflammatory cytokine production in patients with NAFLD. Our aim was to investigate the efficacy of rifaximin on NAFLD.

Methods: Forty-two patients with biopsy-proven NAFLD [15 steatosis, 27 nonalcoholic steatohepatitis (NASH)] were included in this prospective, open-label, observational cohort study. BMI and serum aspartate aminotransferase, alanine aminotransferase (ALT), gamma glutamyl transferase, lipid profile, ferritin, C-reactive protein, glucose, insulin, homeostatic model assessment as well as endotoxin, serum Toll-like receptor 4 (TlR4), interleukin-1α (IL-1α), IL-6, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) levels were measured before and after a 28-day administration of rifaximin (1200 mg/daily). Results were analyzed using nonparametric Wilcoxon signed-rank tests.

Results: A mild reduction in the mean BMI (32.3 ± 6.9 vs. 31.9 ± 6.8, P = 0.02) and a significant reduction in the endotoxin (0.9 ± 0.34 vs. 0.8 ± 0.13, P = 0.03) and IL-10 (4.08 ± 0.9 vs. 3.73 ± 0.7, P = 0.006) levels in the NASH group were noted. A significant reduction was observed in serum aspartate aminotransferase (50.4 ± 39 vs. 33 ± 14, P = 0.01), ALT (72 ± 48 vs. 45.2 ± 26.3, P = 0.0001), gamma glutamyl transferase (52 ± 33 vs. 41.2 ± 21.1, P = 0.02), LDL (137 ± 34 vs. 127 ± 27.5, P = 0.03), and ferritin (142 ± 214 vs. 89.3 ± 123, P = 0.0001) in the NASH group, but only in ALT (50.4 ± 26 vs. 35.5 ± 23.25, P = 0.01), and ferritin (73.6 ± 83 vs. 55 ± 76, P = 0.004) levels decreased significantly in the steatosis group. Treatment with rifaximin did not exert a significant effect on serum levels of TLR-4, IL-1, IL-6, IL-12, or TNF-α in either group.

Conclusion: In NAFLD and especially in NASH, short-term administration of rifaximin appears to be safe and effective.