Pemafibrate as a therapeutic option for metabolic dysfunction-associated steatotic liver disease resistant to dietary intervention.

Aim of the study: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a lifestyle-related disease. However, many patients appear resistant to treatment despite dietary counseling. Pemafibrate is a novel lipidlowering pharmaceutical agent that was developed as a selective peroxisome proliferator-activated receptor α modulator. The present study aimed to clarify the efficacy of pemafibrate in diet-resistant MASLD patients with persistent hyperlipidemia. Material and methods: Participants comprised 91 MASLD patients with persistent alanine aminotransferase (ALT) elevation and hyperlipidemia despite counseling on moderate-carbohydrate restriction (150-200 g/day) for more than one year, who received pemafibrate (0.2 mg/day) for 6 months. Complete response (CR) was defined as ALT normalization (≤ 33 IU/l in males, ≤ 25 IU/l in females). Partial response (PR) was defined as a ≥ 30% reduction in ALT level from baseline, without achieving CR. No response (NR) was defined as achieving neither CR nor PR. Dietary counseling was maintained every 3 months throughout pemafibrate treatment. Results: CR, PR, and NR rates were 40% (36/91), 24% (22/91), and 36% (33/91), respectively. The response rate (CR + PR) was 64%. Although no significant change in body weight was observed, significant reductions were seen in lipid profiles (including triglycerides and low-density lipoprotein cholesterol) and liver enzymes (including ALT, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase). The concentration of glycosylated isomers of Mac-2-binding protein was significantly reduced, but no significant change in liver shear wave velocity was observed. Conclusions: Pemafibrate may be a potential second-line therapeutic option for diet-resistant MASLD patients with hyperlipidemia.