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 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 -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.