Effect of pemafibrate on liver enzymes and shear wave velocity in non-alcoholic fatty liver disease patients

Abstract

Background/AimsPemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. Pemafibrate was reported to reduce ALT in non-alcoholic fatty liver disease (NAFLD) patients, but efficacy was not clearly elucidated due to the small size of previous study populations. Therefore, we explored pemafibrate efficacy in NAFLD patients.MethodsWe retrospectively evaluated pemafibrate efficacy on liver enzymes (n = 132) and liver shear wave velocity (SWV, n = 51) in NAFLD patients who had taken pemafibrate for at least 24 weeks.ResultsPatient ALT levels were decreased from 81.0 IU/L at baseline to 48.0 IU/L at week 24 (P < 0.0001). Serum levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and triglyceride (TG) were significantly decreased, and high-density lipoprotein cholesterol and platelet count were significantly increased, with no change in body weight being observed. Study participant SWV values decreased from 1.45 m/s at baseline to 1.32 m/s at week 48 (P < 0.001). Older age (P = 0.035) and serum TG levels (P = 0.048) were significantly associated with normalized ALT. Changes in AST, ALT, γ-GTP and body weight were significantly correlated with change in SWV.ConclusionPemafibrate significantly improves liver function, serum TG and liver stiffness in NAFLD patients. Pemafibrate is a promising therapeutic agent for NAFLD and may be a candidate for NAFLD patients with elevated TG.

Gamma‐glutamyl transferase predicts pemafibrate treatment response in non‐alcoholic fatty liver disease

“…For example, a randomized trial 19 of 118 patients with magnetic resonance imaging-diagnosed NAFLD, including patients without dyslipidemia, demonstrated that pemafibrate treatment over 72 weeks did not improve magnetic resonance imaging-estimated proton density fat fraction, but it did lead to improvements in ALT and GGT levels and magnetic resonance elastography-based liver stiffness at 48 weeks and at 72 weeks. Several other studies of pemafibrate treatment have reported improved fibrosis using non-invasive tests, including analyses of Mac-2 binding protein glycosylation isomer 20 and shear wave velocity, 16 and the results of these studies support the present results.…”

“…16 In terms of the use of baseline parameters to predict pemafibrate response, age and TG level have been reported to be associated with normalization of ALT. 16 Despite these connections to markers of fibrosis, to our knowledge, few studies have examined factors at baseline that directly contribute to improvement of fibrosis. Over a 6-month pemafibrate treatment, Shinozaki et al reported that age greater than 50 years and BMI less than 25 contributed to reduction of levels of Mac-2 binding protein glycan isomer.…”

“…In addition to our previous studies, 14 several studies have demonstrated that pemafibrate treatment leads to reduction of ALT and TG levels in the context of NAFLD. [15][16][17] Importantly, such studies have consistently shown that pemafibrate administration does not decrease BMI and that the therapeutic effect of pemafibrate is independent of weight loss. For example, a randomized trial 19 of 118 patients with magnetic resonance imaging-diagnosed NAFLD, including patients without dyslipidemia, demonstrated that pemafibrate treatment over 72 weeks did not improve magnetic resonance imaging-estimated proton density fat fraction, but it did lead to improvements in ALT and GGT levels and magnetic resonance elastography-based liver stiffness at 48 weeks and at 72 weeks.…”

“…13 The ability of pemafibrate treatment to lead to improvements of liver function and hepatic fibrosis, as assessed by non-invasive tests, in NAFLD patients has been previously reported. [14][15][16][17] However, these studies did not examine factors that predict the efficacy of long-term pemafibrate administration on the improvement of hepatic fibrosis. Predicting the therapeutic effect of pemafibrate before treatment begins would be useful for personalizing NAFLD treatments for individual patients.…”

Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes

“…In addition, pemafibrate could be a promising therapeutic agent for NAFLD and NASH as well as a candidate for combination therapy with statins or other lipid-lowering drugs. Numerous studies in the literature have demonstrated that pemafibrate significantly improves liver function, serum TG and liver stiffness in NAFLD patients [ 109 ]. Moreover, pemafibrate improves markers of hepatic inflammation and fibrosis regardless of BMI.…”