Concentration-dependent response to pioglitazone in nonalcoholic steatohepatitis

Abstract

Background: Pioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). However, there is marked variability in treatment response. Aim: To evaluate the relationship between concentrations of pioglitazone and its active metabolites and treatment outcomes in patients with NASH. Methods: Pioglitazone concentrations were measured in patients with NASH treated with pioglitazone 45 mg/day for 18 months; liver biopsy samples were obtained at baseline and after treatment. The primary outcome was a ≥2-point reduction in NAFLD activity score (NAS) with at least one-point improvement in more than one liver histology category and without worsening of fibrosis. A novel marker, the pioglitazone exposure index, was calculated to consider the concentrations of pioglitazone as well as the two active metabolites. Results: The response to pioglitazone was concentration-dependent as evidenced by the significant relationship between both pioglitazone concentration and pioglitazone exposure index with changes in NAS (r=.48, P=.0002 and r=.51, P