Aim: Gut microbial dysbiosis is implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy.Methods: Patients with biopsy-proven NASH and elevated aminotransferase values were included in this open-label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6-week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic-euglycemic clamp.Results: Fifteen patients (13 men and 2 women) with a median (range) age of 46 (32-63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in .7-59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30-217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessmentestimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment.Conclusion: These data do not indicate a beneficial effect of rifaximin in patients with NASH.

medications and 8 did not have diabetes. After 6 weeks of therapy, there was no difference in ALT before, 69 (40)IU/L, and after, 71 (43)IU/L, treatment, p = 0.7. Hepatic lipid content was 23.3(12.8)% before and 26.5(15.9)% after Rifaximin, p = 0.16. Peripheral insulin sensitivity (Rd) was unchanged, 29.5 (6.5) to 29.4 (10.0) mmol/kg min, p = 0.91, hepatic insulin sensitivity (% suppression of endogenous glucose production) was unchanged (35.2(10.1)% to 31.2(13.2)%, p = 0.35). There were no significant differences in body mass index, waist and hip circumference, IL 1b, IL6, IL10, IL18, CD14, TNFa, Leptin, Resistin and Adiponectin values with treatment. Conclusion Treatment with Rifaximin was not associated with changes in markers of hepatocellular damage, hepatic lipid content, cytokine profile or insulin sensitivity in patients with NASH.

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