Pemafibrate Ameliorates Liver Dysfunction and Fatty Liver in Patients with Non-Alcoholic Fatty Liver Disease with Hypertriglyceridemia: A Retrospective Study with the Outcome after a Mid-Term Follow-Up

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27–81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56–157 weeks). Serum triglyceride was significantly decreased by −41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by −42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), −57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and −43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia.

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

“…For the first time, our study revealed that pemafibrate treatment led to a decrease in liver stiffness when assessed using SWE, however Nakajima et al reported that pemafibrate showed a significant reduction in liver stiffness using another instrument, magnetic resonance elastography, in a double-blind, phase 2 study in patients with NAFLD ( 11 ). We demonstrated that the change in liver stiffness was accompanied with a significant improvement in blood liver fibrosis markers such as Plt count and FIB-4 index, which was consistent with previous reports ( 11 , 15 , 17 , 18 , 21 ). The significant reduction in liver stiffness and fibrosis markers suggests an overall improvement in liver fibrosis, indicating that pemafibrate may have another advantage in treating patients with liver fibrosis, since liver fibrosis is associated with an increased risk of developing liver-related events and is predictive in NAFLD patient prognosis ( 29 ).…”

Higher Responsiveness for Women, High Transaminase Levels, and Fat Percentage to Pemafibrate Treatment for NAFLD

“…They also observed ameliorated FibroScan-AST score in 10 patients with NAFLD during PEM treatment, which correlated with ALT changes and demonstrated the hepatic anti-inflammatory effect of PEM [ 27 ]. Ikeda et al reported that PEM significantly decreased TG and ALT in 16 NAFLD patients, with fatty liver improvement in some cases [ 28 ]. Nakajima et al evaluated the efficacy and safety of PEM in 58 patients with NAFLD in a placebo-controlled study and found that while treatment for 18 months did not reduce liver fat content, it significantly decreased magnetic resonance elastography-measured liver stiffness [ 29 ].…”

Effect of a combination of pemafibrate and a mild low‐carbohydrate diet on obese and non‐obese patients with metabolic‐associated fatty liver disease

“…14 As for previous studies of hepatic steatosis, Ikeda et al reported improvement in liver steatosis (39.1 ∓ 1.2 to 57.8 ∓ 2.7 HU, P = 0.028) and liver/spleen ratio (0.76 ∓ 0.04 to 1.18 ∓ 0.02, P = 0.012), but only three cases were included in the study. 23 Hatanaka et al showed no significant improvement in CAP using Fibroscan, 25 and Nakajima et al reported no evident improvement observed by MRI-PDFF. 14 Collectively, most studies to date have reported improvement in fibrosis/stiffness, but improvement in steatosis is not definitive when pemafibrate is used alone for fatty liver disease.…”

“…As for previous studies of hepatic steatosis, Ikeda et al . reported improvement in liver steatosis (39.1 ∓ 1.2 to 57.8 ∓ 2.7 HU, P = 0.028) and liver/spleen ratio (0.76 ∓ 0.04 to 1.18 ∓ 0.02, P = 0.012), but only three cases were included in the study 23 . Hatanaka et al .…”