First-in-Asian double-blind randomized trial to assess the efficacy and safety of insulin sensitizer in nonalcoholic steatohepatitis patients

Background The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. Aims The double-blind, randomized, placebo-controlled trial was conducted aiming to investigate the efficacy and safety of pioglitazone in NASH patients. Methods A total of 90 NASH patients (66 males, age = 44.1 +/- 12.7 years) were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. The primary endpoint was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening was also evaluated. Results At EOT, there was a significantly decline of alanine aminotransferase (86.9 +/- 34.3 to 45.7 +/- 35.8 IU/L, p = 0.003) level in Arm A patients. In intention-to-treat analysis among 66 patients who completed paired biopsies, The NAFLD activity score (NAS) of 30 Arm A patients significantly decreased from 4.27 +/- 1.14 at baseline to 2.53 +/- 1.63 at EOT (p < 0.0001), whereas there was no significant change in patients of Arm B (3.94 +/- 1.41 vs 3.94 +/- 1.51, p = 1.0). NASH improvement without worsening of fibrosis was achieved in 46.7% (14/30) patients in Arm A, compared to 11.1% (4/36) patients in Arm B (p = 0.002). Liver fat content reduced (20.2 +/- 9.0 to 14.3 +/- 6.9%, p < 0.0001) on MRI-PDFF in Arm A compared to their counterparts. No significant difference of adverse events occurred between groups. Conclusions A 24-week pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444)