Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study

Thursz, Mark R.; Cobbold, Jeremy F.L.; Atkinson, Stephen; Marchesi, Julian R.; Smith, Ann; Wai, Sann N.; Stove, Julie; Yee, Michael S.; Anstee, Quentin M.; Goldin, Robert D.; Taylor-Robinson, Simon D.; Bell, Jimmy D.; Holmes, Elaine; Shojaee-Moradie, Fariba; Thomas, E. Louise; Jackson, Nicola; Fitzpatrick, Julie; Umpleby, A. Margot

Abstract

© 2017 The Japan Society of Hepatology. 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 6weeks rifaximin 400mg twice daily, followed by a 6-week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6weeks 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 6weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 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]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12weeks from baseline, serum ALT increased to 83 (30–217)IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated 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.

• Journal Article Type: Article
• Acceptance Date: Apr 8, 2017
• Online Publication Date: May 31, 2017
• Publication Date: Jan 1, 2018
• Deposit Date: Oct 2, 2019
• Publicly Available Date: Oct 4, 2019
• Journal: Hepatology Research
• Print ISSN: 1386-6346
• Electronic ISSN: 1872-034X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 1
• Pages: 69-77
• DOI: https://doi.org/10.1111/hepr.12904
• Keywords: Hepatology; Infectious Diseases
• Public URL: https://uwe-repository.worktribe.com/output/3452929
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.12904
• Related Public URLs: https://spiral.imperial.ac.uk:8443/handle/10044/1/61812