OS-37
The First-in-Asian Double-blind Randomized Trial to Assess the Efficacy and Safety of Insulin Sensitizer in Non-alcoholic Steatohepatitis

Jee-Fu Huang, Chia-Yen Dai, Chung-Feng Huang, Ming-Lun Yeh, Ming-Lung Yu, Wan-Long Chuang

Kaohsiung Medical University Hospital, Hepatobiliary Division, Department of Internal Medicine, Taiwan, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Department of Internal Medicine, Taiwan
Email: jfliver@kmu.edu.tw

Background and aims: The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. We conducted a double-blind, randomized, placebo-controlled trial of insulin sensitizer in Taiwanese NASH patients. The primary end point was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening were also evaluated.

Method: A total of 90 eligible Taiwanese NASH patients (66 males, age = 44.1 ± 12.7 years) were recruited from April 2009 to August 2019. They were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. They received paired biopsies and MRI-PDFF examinations before randomization and at EOT.

Results: Diabetes, dyslipidemia, and metabolic syndrome were found in 21 (23.3%), 56 (62.2%), and 52 (57.8%) of the patients, respectively. The mean fat content on MRI-PDFF was 21.2 ± 8.4%, whereas the mean NAS was 4.3 ± 1.3. The pre-treatment mean ALT level was 90.0 ± 39.4 IU/L in 41 Arm A patients, and it significantly decreased to 45.7 ± 35.8 IU/L at EOT (p = 0.003). By contrast, there were no significant changes of ALT level (90.3 ± 39.0 IU/L to 79.8 ± 48.0 IU/L) in 46 patients of Arm B. In an intention-to-treat analysis, 66 patients who received at least one dose and completed paired biopsies were recruited into further analysis. 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). 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. 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). No significant difference of adverse events occurred between groups.

Conclusion: A 24-weeks pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444)