Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease
Tüzün İnce, Ali
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CitationGangarapu, V., Tüzün İnce, A., Baysal, B., Kayar, Y., Kılıç, Ü., Gök, Ö. ... Şentürk, H. (2015). Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. European Journal of Gastroenterology and Hepatology, 27(7), 840-845. https://dx.doi.org/10.1097/MEG.0000000000000348
ObjectiveRecent 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.MethodsForty-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-1 (IL-1), IL-6, IL-10, IL-12, and tumor necrosis factor- (TNF-) levels were measured before and after a 28-day administration of rifaximin (1200mg/daily). Results were analyzed using nonparametric Wilcoxon signed-rank tests.ResultsA mild reduction in the mean BMI (32.36.9 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- in either group.ConclusionIn NAFLD and especially in NASH, short-term administration of rifaximin appears to be safe and effective.