Abstract

Background: Despite advances in understanding the pathophysiology of nonalcoholic steatohepatitis (NASH), no pharmacotherapy has been proven effective in improving outcome. Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors with key role in metabolic homeostasis and inflammation and PPAR knockout mice are susceptible to development of NASH. Studies have shown protective role of PPAR-α in hepatic steatosis and inflammation and PPAR-γ as insulin sensitizers. Saroglitazaar is dual PPAR α and γ agonist approved for diabetic dyslipidemia Though the drug is approved in India for use in patients with NASH, data regarding improvement in liver fibrosis is still awaited. We compared saroglitazaar alone versus its combination with vitamin E in patients with NASH.

Methods: This was a prospective, randomized, open label clinical trial conducted from July 2021 to December 2022 in a tertiary care center. The study was approved by institutional ethics committee and registered on CTRI vide registration no CTRI/2021/07/034946. All patients of biopsy proven NASH were randomized in 1:1 allocation ratio to receive saroglitazaar 4 mg OD (Group I) or saroglitazaar 4 mg OD with Vitamin E 400 IU OD (Group II) for a period of 6 months. The primary end points were improvement in NAS score, liver stiffness measurement (LSM) values by transient elastography and liver enzymes (SGPT). The secondary end points were improvement in BMI and serum triglycerides (TG) and cholesterol (Chol) levels.

Results: Total 53 patients were enrolled, two patients in Group I were lost to follow up and finally, Group I (n=25) and Group II (n=26) were analysed. All baseline characteristics were comparable between two groups. In primary end points, LSM values improved in group I (9.1 to 7.0 kPa, P=0.03), Group II (7.9 to 7.1 kPa, P=0.04), SGPT values improved in Group I (101 to 81 U/L, P=0.02), Group II (98 to 75 U/L, P=0.04) significantly with no change in NAS score in both the groups from baseline to 24 weeks respectively. In secondary end points, significant reduction in TG and Chol in Group I (234 to 167 mg/dL, P=0.003; 234 to 199 mg/dL, P=0.04), Group II (223 to 188 mg/dL, P=0.04; 229 to 189 mg/dL, P=0.007) respectively with no change in BMI.

Conclusion: Saroglitazaar alone was effective in improving LSM and SGPT values in NASH. However, no improvement in NAS score could be observed over a period of 24 weeks.