Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study

Abstract

Aim: No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD.

Methods: Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers.

Results: A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns.

Conclusions: Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.

Keywords: Hepatic fibrosis; Hepatic function; Metabolic dysfunction-associated steatotic liver disease; Omega-3-acid ethyl ester; Pemafibrate.

Fig.1.

Study flow chart showing patient enrollment, allocation, and analysis

Fig.2. Changes in hepatic enzymes

A two-sample t-test was performed for the intergroup comparison of measurements. Because the γ-GTP measurements were not distributed normally, a two-sample t-test was performed using log-transformed values. The adjusted mean change in each continuous variable was estimated using analysis of covariance (ANCOVA), with the treatment groups as the fixed effect and with the baseline ALT and TG levels and medical institutions as the covariates. ^＊, ^＊＊, and ^＊＊＊ represent p＜0.05, p＜0.01, and p＜0.001, respectively. ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GTP, gamma-glutamyl transpeptidase; TG, triglyceride.

Fig.3. Changes in lipid profiles

A two-sample t-test was performed for the intergroup comparison of measurements. Because the TG measurements were not distributed normally, a two-sample t-test was performed using log-transformed values. The adjusted mean change in each continuous variable was estimated using analysis of covariance (ANCOVA), with the treatment groups as the fixed effect and with the baseline ALT and TG levels and medical institutions as the covariates. ^＊, ^＊＊, and ^＊＊＊ represent p＜0.05, p＜0.01, and p＜0.001, respectively. TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.