Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose

<b>Background and Aim:</b> Controlling the hepatic inflammation of metabolic dysfunction-associated steatotic liver disease (MASLD) is important to prevent serious condition. Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, has demonstrated effectiveness a...

Full description

Saved in:
Bibliographic Details
Main Authors: Satoshi Shinozaki, Kouichi Miura, Toshiyuki Tahara, Hironori Yamamoto
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/15/2/100
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850080631855251456
author Satoshi Shinozaki
Kouichi Miura
Toshiyuki Tahara
Hironori Yamamoto
author_facet Satoshi Shinozaki
Kouichi Miura
Toshiyuki Tahara
Hironori Yamamoto
author_sort Satoshi Shinozaki
collection DOAJ
description <b>Background and Aim:</b> Controlling the hepatic inflammation of metabolic dysfunction-associated steatotic liver disease (MASLD) is important to prevent serious condition. Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, has demonstrated effectiveness at a standard dose (0.2 mg daily). The aim of this study is to evaluate the effectiveness of pemafibrate dose escalation from 0.2 mg to 0.4 mg daily in patients with MASLD who are refractory to standard-dose therapy. <b>Methods:</b> This study included patients with MASLD who had a persistent elevation of alanine aminotransferase (ALT) levels despite more than one year of standard-dose pemafibrate therapy (0.2 mg daily). All patients underwent dose escalation to 0.4 mg once daily. Hepatic inflammation was assessed using serum ALT levels, hepatic function was evaluated with the albumin–bilirubin score, and hepatic fibrosis was estimated using Mac-2 binding protein glycosylation isomer (M2BPGi) levels. A one-year treatment period was investigated, including six months before dose escalation and six months after dose escalation. <b>Results:</b> Eleven patients were included. The median treating period with standard-dose pemafibrate was 3.2 years. Weight did not show significant change throughout the observation period. Regarding the hepatobiliary enzyme, the aspartate aminotransferase, ALT, and γ-glutamyl transpeptidase levels significantly improved six months after the dose escalation. Specifically, ALT improved in all patients, and the ALT levels normalized in four patients (36%). The lipid profiles, the albumin–bilirubin score, and M2BPGi did not significantly change after the dose escalation. <b>Conclusions:</b> The dose escalation of pemafibrate from 0.2 mg to 0.4 mg daily may improve hepatic inflammation in patients with MASLD refractory to standard-dose therapy.
format Article
id doaj-art-dbca4a8f19cc441fb3ec9dc311b0de1c
institution DOAJ
issn 2218-1989
language English
publishDate 2025-02-01
publisher MDPI AG
record_format Article
series Metabolites
spelling doaj-art-dbca4a8f19cc441fb3ec9dc311b0de1c2025-08-20T02:44:53ZengMDPI AGMetabolites2218-19892025-02-0115210010.3390/metabo15020100Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard DoseSatoshi Shinozaki0Kouichi Miura1Toshiyuki Tahara2Hironori Yamamoto3Shinozaki Medical Clinic, Utsunomiya 321-3223, JapanDepartment of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke 329-0431, JapanSaiseikai Utsunomiya Hospital, Utsunomiya 321-0974, JapanDepartment of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke 329-0431, Japan<b>Background and Aim:</b> Controlling the hepatic inflammation of metabolic dysfunction-associated steatotic liver disease (MASLD) is important to prevent serious condition. Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, has demonstrated effectiveness at a standard dose (0.2 mg daily). The aim of this study is to evaluate the effectiveness of pemafibrate dose escalation from 0.2 mg to 0.4 mg daily in patients with MASLD who are refractory to standard-dose therapy. <b>Methods:</b> This study included patients with MASLD who had a persistent elevation of alanine aminotransferase (ALT) levels despite more than one year of standard-dose pemafibrate therapy (0.2 mg daily). All patients underwent dose escalation to 0.4 mg once daily. Hepatic inflammation was assessed using serum ALT levels, hepatic function was evaluated with the albumin–bilirubin score, and hepatic fibrosis was estimated using Mac-2 binding protein glycosylation isomer (M2BPGi) levels. A one-year treatment period was investigated, including six months before dose escalation and six months after dose escalation. <b>Results:</b> Eleven patients were included. The median treating period with standard-dose pemafibrate was 3.2 years. Weight did not show significant change throughout the observation period. Regarding the hepatobiliary enzyme, the aspartate aminotransferase, ALT, and γ-glutamyl transpeptidase levels significantly improved six months after the dose escalation. Specifically, ALT improved in all patients, and the ALT levels normalized in four patients (36%). The lipid profiles, the albumin–bilirubin score, and M2BPGi did not significantly change after the dose escalation. <b>Conclusions:</b> The dose escalation of pemafibrate from 0.2 mg to 0.4 mg daily may improve hepatic inflammation in patients with MASLD refractory to standard-dose therapy.https://www.mdpi.com/2218-1989/15/2/100non-alcoholic fatty liver diseasenon-alcoholic steatohepatitispemafibratedyslipidemiametabolic dysfunction-associated steatotic liver disease
spellingShingle Satoshi Shinozaki
Kouichi Miura
Toshiyuki Tahara
Hironori Yamamoto
Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
Metabolites
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
pemafibrate
dyslipidemia
metabolic dysfunction-associated steatotic liver disease
title Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
title_full Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
title_fullStr Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
title_full_unstemmed Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
title_short Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose
title_sort effectiveness of pemafibrate dose escalation on metabolic dysfunction associated steatotic liver disease refractory to standard dose
topic non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
pemafibrate
dyslipidemia
metabolic dysfunction-associated steatotic liver disease
url https://www.mdpi.com/2218-1989/15/2/100
work_keys_str_mv AT satoshishinozaki effectivenessofpemafibratedoseescalationonmetabolicdysfunctionassociatedsteatoticliverdiseaserefractorytostandarddose
AT kouichimiura effectivenessofpemafibratedoseescalationonmetabolicdysfunctionassociatedsteatoticliverdiseaserefractorytostandarddose
AT toshiyukitahara effectivenessofpemafibratedoseescalationonmetabolicdysfunctionassociatedsteatoticliverdiseaserefractorytostandarddose
AT hironoriyamamoto effectivenessofpemafibratedoseescalationonmetabolicdysfunctionassociatedsteatoticliverdiseaserefractorytostandarddose