Rifaximin in Non-Alcoholic Steatohepatitis: An Open-Label Pilot Study

Cobbold, J.F.L., Atkinson, S., Marchesi, J.R., Smith, A., Wai, S.N., Stove, J., Shojaee-Moradie, F., Jackson, N.C., Umpleby, A.M., Fitzpatrick, J., Thomas, E.L., Bell, J.D., Holmes, E., Taylor-Robinson, S.D., Goldin, R.D., Yee, M.S., Anstee, Q.M. and Thursz, M.R. (2017) Rifaximin in Non-Alcoholic Steatohepatitis: An Open-Label Pilot Study. Hepatology Research. ISSN 1386-6346 (In Press)

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Official URL: https://dx.doi.org/10.1111/hepr.12904

Abstract

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 ALT after 6 weeks of Rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinaemic euglycaemic clamp. Results Fifteen patients, 13 male, 2 female, with median (range) age 46(32-63) years were included. Seven had diabetes on oral hypoglycaemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33-191] versus 63 [41-218]IU/L, p = 0.41), peripheral glucose uptake (28.9 [19.4-48.3] to 25.5 [17.7-47.9] µmol/kg/min, p = 0.30), hepatic insulin sensitivity (35.2 [15.3-51.7]% versus 30.0 [10.8-50.5]%, p = 0.47), or hepatic lipid content (21.6[2.2-46.2]% before and 24.8[1.7-59.3]% after Rifaximin, 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 HOMA-IR (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 faecal microbiota with treatment. Conclusion These data do not indicate a beneficial effect of Rifaximin in patients with NASH.

Item Type: Article
Uncontrolled Keywords: Antibiotic;Hippurate; Insulin resistance;Microbiota;NAFLD;Non-alcoholic steatohepatitis ;
Subjects: University of Westminster > Science and Technology
SWORD Depositor: repository@westminster.ac.uk
Depositing User: repository@westminster.ac.uk
Date Deposited: 27 Apr 2017 11:54
Last Modified: 26 Sep 2017 14:44
URI: http://westminsterresearch.wmin.ac.uk/id/eprint/18947

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