title: 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.
  
  
  CONCLUSIONS
  In NAFLD and especially in NASH, short-term administration of rifaximin appears to be safe and effective.
authors.affiliation: Departments of aGastroenterology bMedical Biology, Faculty of Medicine, Istanbul Medipol University cDepartment of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Venkatanarayana
authors.initials: V
authors.lastname: Gangarapu
authors.forename: Ali Tüzün
authors.initials: AT
authors.lastname: Ince
authors.forename: Birol
authors.initials: B
authors.lastname: Baysal
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Kayar
authors.forename: Ulkan
authors.initials: U
authors.lastname: Kılıç
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Gök
authors.forename: Ömer
authors.initials: Ö
authors.lastname: Uysal
authors.forename: Hakan
authors.initials: H
authors.lastname: Şenturk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D012294:Rifamycins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000078262:Rifaximin