Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study
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OA Location
Author(s)
Type
Journal Article
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 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 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 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 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.
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 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 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 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.
Date Issued
2018-01-01
Date Acceptance
2017-04-08
Citation
HEPATOLOGY RESEARCH, 2018, 48 (1), pp.69-77
ISSN
1386-6346
Publisher
WILEY
Start Page
69
End Page
77
Journal / Book Title
HEPATOLOGY RESEARCH
Volume
48
Issue
1
Copyright Statement
© 2017 The Japan Society of Hepatology. This is the accepted version of the following article: Cobbold, J. F. L., Atkinson, S., Marchesi, J. R., Smith, A., Wai, S. N., Stove, J., Shojaee‐Moradie, F., Jackson, N., 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. (2018) Rifaximin in non‐alcoholic steatohepatitis: An open‐label pilot study. Hepatol Res, 48: 69–77. doi: 10.1111/hepr.12904, which has been published in final form at https://dx.doi.org/10.1111/hepr.12904
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000419347800009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
antibiotic
hippurate
insulin resistance
microbiota
NAFLD
non-alcoholic steatohepatitis
FATTY LIVER-DISEASE
GUT MICROBIOTA
INSULIN SENSITIVITY
METABOLIC SYNDROME
ACID METABOLISM
INFLAMMATION
HIPPURATE
CIRRHOSIS
ENDOTOXEMIA
VANCOMYCIN
Publication Status
Published
Date Publish Online
2017-05-31