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: