Skip to main content


Log in

Identification and Characterization of Fenofibrate-Induced Liver Injury

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript



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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others



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


  1. Assmann G, Schulte H, von Eckardstein A. Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am J Cardiol. 1996;77:1179.

    Article  CAS  PubMed  Google Scholar 

  2. Dewey FE, Gusarova V, O’Dushlaine C, et al. Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med. 2016;374:1123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med.. 2016;374:1134.

    Article  PubMed Central  Google Scholar 

  4. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1.

    Article  PubMed  Google Scholar 

  5. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849.

    Article  CAS  PubMed  Google Scholar 

  6. Jackevicius CA, Tu JV, Ross JS, et al. Use of fibrates in the United States and Canada. JAMA. 2011;305:1217–1224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ganne-Carrié N, de Leusse A, Guettier C, et al. Autoimmune hepatitis induced by fibrates. Gastroenterol Clin Biol. 1998;22:525–529.

    PubMed  Google Scholar 

  8. Dohmen K, Wen CY, Nagaoka S, et al. Fenofibrate-induced liver injury. World J Gastroenterol. 2005;11:7702–7703.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lucena MI, Andrade RJ, Vicioso L, et al. Prolonged cholestasis after raloxifene and fenofibrate interaction: a case report. World J Gastroenterol. 2006;12:5244–5246.

    PubMed  PubMed Central  Google Scholar 

  10. Ho CY, Kuo TH, Chen TS, et al. Fenofibrate-induced acute cholestatic hepatitis. J Chin Med Assoc. 2004;67:245–247.

    PubMed  Google Scholar 

  11. Hajdu D, Aiglová K, Vinklerová I, et al. Acute cholestatic hepatitis induced by fenofibrate. J Clin Pharm Ther. 2009;34:599–602.

    Article  CAS  PubMed  Google Scholar 

  12. Rodríguez-Vilarrupla A, Laviña B, García-Calderó H, et al. PPARα activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats. J Hepatol. 2012;56:1033–1039.

    Article  PubMed  Google Scholar 

  13. Montagner A, Polizzi A, Fouché E, et al. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut. 2016;65:1202–1214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hegade VS, Khanna A, Walker LJ, et al. Long-term fenofibrate treatment in primary biliary cholangitis improves biochemistry but not the UK-PBC risk score. Dig Dis Sci. doi:10.1007/s10620-016-4250-y. 2016 Jul 19. [Epub ahead of print].

  15. Cheung AC, Lapointe-Shaw L, Kowgier M, et al. Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. Aliment Pharmacol Ther. 2016;43:283–293.

    Article  CAS  PubMed  Google Scholar 

  16. Rockey DC, Seeff LB, Rochon J, et al. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel–Uclaf causality assessment method. Hepatology. 2010;51:2117–2126.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Benichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs–II. An original model for validation of drug causalityassessment methods: case reports with positive rechallenge. J Clin Epidemiol. 1993;46:1331–1336.

    Article  CAS  PubMed  Google Scholar 

  18. Fontana RJ, Watkins PB, Bonkovsky HL, et al. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf.. 2009;32:55–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kleiner DE, Chalasani NP, Lee WM, et al. Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014;59:661–670.

    Article  PubMed  Google Scholar 

  20. Fontana RJ, Hayashi PH, Barnhart H, et al. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015;110:1450–1459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chalasani N, Bonkovsky HL, Fontana R, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148:1340–1352.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nicoletti P, Aithal GP, Bjornsson ES, et al. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a Genome-Wide Association study. Gastroenterology. 2017;152:1078–1089.

    Article  CAS  PubMed  Google Scholar 

  23. Patterson AD, Shah YM, Matsubara T, et al. Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity. Hepatology. 2012;56:281–290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Moustafa T, Fickert P, Magnes C, et al. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury. Gastroenterology. 2012;142:140–151.

    Article  CAS  PubMed  Google Scholar 

  25. Accessed 2 May 2017.

Download references


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 information

Authors and Affiliations



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.

Corresponding author

Correspondence to Jawad Ahmad.

Ethics declarations

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, J., Odin, J.A., Hayashi, P.H. et al. Identification and Characterization of Fenofibrate-Induced Liver Injury. Dig Dis Sci 62, 3596–3604 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: