Digestive Diseases and Sciences

, Volume 62, Issue 12, pp 3596–3604 | Cite as

Identification and Characterization of Fenofibrate-Induced Liver Injury

  • Jawad Ahmad
  • Joseph A. Odin
  • Paul H. Hayashi
  • Naga Chalasani
  • Robert J. Fontana
  • Huiman Barnhart
  • Elizabeth T. Cirulli
  • David E. Kleiner
  • Jay H. Hoofnagle
Original Article



Fenofibrate is a commonly used hypolipidemic associated with rare instances of hepatotoxicity, and routine liver biochemistry monitoring is recommended.


The aim of this study is to describe the presenting clinical features, liver histopathology, and outcomes of 7 cases of acute liver injury associated with fenofibrate.


All cases of definite, very likely, and probable drug-induced liver injury (DILI) attributed to fenofibrate enrolled in the DILI Network study between 2004 and 2015 were reviewed.


Among 1229 patients with confirmed DILI, 7 cases (0.6%) were attributed to fenofibrate. The median age was 43 (range 37–61) years, and latency to onset was short (5–8 weeks) in 4 patients but more prolonged (18–56 weeks) in the rest. Laboratory results at presentation showed hepatocellular, mixed, and cholestatic injury, but 6 cases presented with jaundice. No patient had undergone routine monitoring. Four patients required hospitalization and 2 in whom drug discontinuation was delayed had a severe outcome, 1 undergoing liver transplantation, and 1 developing chronic injury and death. Liver biopsy was available in 4 patients and showed diverse injury patterns. Genetic studies showed the presence of the rare HLA-A*33:01 in 3 patients (43 vs. 1% in control populations). The causality scores were highly likely in 5 and probable in 2.


Liver injury after fenofibrate exposure occurs with variable latency, enzyme elevation, and histology. Although most cases are self-limited, severe injury and mortality can occur, particularly if drug withdrawal is delayed. Jaundice or abnormal laboratory tests during fenofibrate therapy should trigger prompt discontinuation.


Fenofibrate Hepatotoxicity Liver injury tests 



Alanine aminotransferase


Antinuclear antibody

Alk P

Alkaline phosphatase


Aspartate aminotransferase


Drug-induced liver injury


Drug Induced Liver Injury Network


International normalized ratio


Roussel Uclaf Causality Assessment Method


Upper limit of normal



The Drug-Induced Liver Injury Network (DILIN) is structured as an U01 cooperative agreement supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) with funds provided by the following Grants: U01DK065211 (Indiana University [Purdue]), U01DK065184 (University of Michigan [Ann Arbor]), U01DK065201 (University of North Carolina [Chapel Hill], Asheville, Wake Forest Baptist Medical Center), U01DK083020 (University of Southern California, University of California-Los Angeles [Pfleger Liver Institute]), U01DK083027 (Albert Einstein Medical Center), U01DK100928 (Icahn School of Medicine at Mount Sinai), U01DK065176 (Duke Clinical Research Institute). Additional support was provided by the Intramural Division of the National Cancer Institute (NCI), NIH.

Author’s Contribution

All authors contributed to the collection of clinical data, data analysis, and initial and final drafting of the manuscript. DEK provided expert review of the available liver histopathology.

Compliance with ethical standards

Conflict of interest

Dr. Chalasani has ongoing consulting activities (or had in the preceding 12 months) with NuSirt, Abbvie, Eli Lilly, Afimmune (DS Biopharma), Tobira (Allergan), Madrigal, Shire, Cempra, Ardelyx, Gen Fit and Amarin. These consulting activities are generally in the areas of nonalcoholic fatty liver disease and drug hepatotoxicity. Dr. Chalasani receives research grant support from Intercept, Lilly, Gilead, Galectin Therapeutics and Cumberland where his institution receives the funding. Over the last decade, Dr. Chalasani has served as a paid consultant to more than 30 pharmaceutical companies, and these outside activities have regularly been disclosed to his institutional authorities. Drs. Kleiner and Hoofnagle have no conflicts of interest to disclose.

Supplementary material

10620_2017_4812_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Jawad Ahmad
    • 1
  • Joseph A. Odin
    • 1
  • Paul H. Hayashi
    • 1
  • Naga Chalasani
    • 1
  • Robert J. Fontana
    • 1
  • Huiman Barnhart
    • 1
  • Elizabeth T. Cirulli
    • 1
  • David E. Kleiner
    • 1
  • Jay H. Hoofnagle
    • 1
  1. 1.Division of Liver DiseasesIcahn School of Medicine at Mount SinaiNew YorkUSA

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