Impact of Saroglitazar on Liver Stiffness Measurements in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) With Compensated Cirrhosis: A Single-Arm Study

TL;DR

This study examines the effects of Saroglitazar on liver stiffness in patients with a specific type of liver disease and finds it to be safe with some improvements in liver health markers.

Contribution

The study provides new insights into the safety and effects of Saroglitazar in MASLD with compensated cirrhosis.

Findings

Saroglitazar reduced liver fat content and improved several biochemical markers in patients with MASLD-CC.

Liver stiffness measurements showed a slight decrease, but changes were not significantly different between groups.

The drug was generally safe, with only minor adverse events reported.

Abstract

Background

Saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, shows promise in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its impact and safety in MASLD with compensated cirrhosis (MASLD-CC) remain relatively unexplored.

Methods

In a single-center, single-arm retrospective study, we assessed the impact of Saroglitazar (4 mg for 24 weeks) on liver stiffness measurement (LSM) by magnetic resonance elastography (MRE) in MASLD-CC and evaluated safety and effects on biochemical indices and liver fat content (LFC) by MRI-proton density fat fraction (MRI-PDFF). To distinguish measurement error from true change, a threshold of 0.75 kPa for MRE-LSM was used to categorize LSM progressors and regressors.

Results

Twenty-six patients with MASLD-CC (age 61 (58-64) years; 61.5% female; BMI 28.7 ± 3.3 kg/m²; 88.4% obese; 76.9% with diabetes) completed 24 weeks of follow-up. Body weight (69.5 (64-75) vs 68.3 (66-71) kg, p = 0.02), alanine transaminase (42.5 (30-61) vs 22.5 (20-36) U/L), aspartate transaminase (53 (39-74) vs 40 (33-49) U/L), fasting blood sugar (109 (100-129.5) vs 100.5 (96.3-108.3) mg/dL), total cholesterol (157 (139.5-171) vs 140 (120-167) mg/dL), triglycerides (121 (95-153) vs 100 (94-113.5) mg/dL), and LFC (7.2 (6.9-11.1) vs 5.1 (3.5-6.1) %) decreased with Saroglitazar (p < 0.01 for all). A decrease in MRE-LSM (5.4 (4.9-6.2) vs 5.1 (4.9-5.8) kPa) was seen in the overall cohort (p = 0.04). However, only 4 (15.3%) and 2 (7.6%) showed MRE-LSM regression and progression of ≥ 0.75 kPa, respectively. No differences were noted between regressors and progressors using the 0.75 kPa threshold (23.5% vs 22.2%, p = 0.91). Two patients (pruritus and increased urine frequency) reported adverse events.

Conclusion

Saroglitazar use over 24 weeks in MASLD-CC appears safe. Using pragmatic thresholds, changes in liver stiffness over 24 weeks did not differ significantly. Larger prospective studies with longer follow-up are warranted.

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