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HERO ID
4777290
Reference Type
Journal Article
Subtype
Review
Title
Peroxisome proliferator-activated receptor alpha-mediated drug toxicity in the liver
Author(s)
Hedrington, MS; Davis, SN
Year
2018
Is Peer Reviewed?
Yes
Journal
Expert Opinion on Drug Metabolism & Toxicology
ISSN:
1742-5255
EISSN:
1744-7607
Volume
14
Issue
7
Page Numbers
671-677
Language
English
PMID
29847748
DOI
10.1080/17425255.2018.1483337
Abstract
INTRODUCTION:
Drug-induced hepatic injury is the most common cause of acute liver failure in the United States. Peroxisome proliferator-activated receptor alpha (PPARα)-mediated drugs are included among the approximately 900 natural and synthetic substances, which have shown hepatotoxicity. Areas covered: This review will focus on fibrates - PPARα agonists and their implication in causing liver injury. Expert opinion: Compelling evidence for fibrate-induced hepatotoxicity is not available. Results have been varying because several large randomized clinical trials have reported similar elevations of plasma transaminase levels in fibrate or placebo treated groups. On the other hand, one meta-analysis has reported an increased risk of hepatotoxicity when fibrates are combined with statins. Fibrate induced clinically apparent liver damage has been demonstrated in case reports. However, there is a wide spectrum of clinical phenotypic presentations of these cases (onset of injury, pattern of enzyme elevation and resolution of the symptoms), which reduces the ability to identify specific cause and effect of any putative fibrate-induced hepatotoxicity. Thus, the current recommendations for using fibrates include monitoring of aminotransferase levels especially if combined with statins and discontinuation of the treatment only if the levels persist above three times the upper limit of normal.
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