A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL.

BACKGROUND AND AIM: Vitamin E is widely prescribed for non-alcoholic steatohepatitis (NASH). Saroglitazar, a novel dual peroxisome proliferator-activator receptor ɑ/γ agonist, is approved in India for non-alcoholic fatty liver disease (NAFLD). No head-to-head comparative study for vitamin E and saroglitazar is available. We studied the efficacy and safety of saroglitazar and vitamin E in NAFLD/NASH.

MATERIALS AND METHODS: We prospectively randomised 175 NAFLD patients into four arms as Saroglitazar 4 mg daily alone (n = 44), vitamin E 800IU daily alone (n = 41), vitamin E and saroglitazar combination (n = 47), and control arm (n = 43). All the baseline variables including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were recorded. Reassessment was done after 24 weeks of treatment.

RESULTS: The mean age and body mass index was 45 ± 11 years and 26 ± 3.6 kg/m2 , respectively. Compared to control, the decrease in alanine amino transferase levels with saroglitazar, vitamin E, and combination therapy was significant (95% confidence interval [CI]: 6.27-28.25, P  = 0.002, 95% CI: -3.39 to 18.88, P  = 0.047 and 95% CI: 8.10-29.54, P  = 0.001, respectively). The reduction in CAP was significant with saroglitazar and combination therapy (95% CI: -31.94 to 11.99, P  = 0.015 and 95% CI: -10.48 to 30.51, P  = 0.026, respectively). Only combination therapy shows significant reduction in LSM (95% CI: 0.41-1.68, P  = 0.001). Among glycaemic parameters, both saroglitazar alone and combination therapy significantly improved glycosylated haemoglobin levels ( P  = 0.001 and P  = 0.015, respectively), and only combination therapy significantly improved homoeostasis model assessment-estimated insulin resistance ( P  = 0.047). Saroglitazar alone showed significant reduction in triglyceride and low-density lipoprotein levels ( P  = 0.038 and P  = 0.018, respectively), and combination therapy showed significant increase in high-density lipoprotein levels ( P  = 0.024).

CONCLUSIONS: Combination of Saroglitazar and vitamin E showed statistically significant reduction of LSM and CAP along with biochemical, glycaemic, and lipid parameters.

CLINICAL TRIAL REGISTRY INDIA NO: CTRI/2022/01/039538.