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Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series

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An Erratum to this article was published on 06 October 2016

Abstract

Background/Aim

Herbal and dietary supplement (HDS) hepatotoxicity is increasingly being reported in the USA. This case series describes the presenting clinical features and outcomes of seven patients with liver injury attributed to OxyELITE Pro enrolled in the Drug-Induced Liver Injury Network (DILIN) study.

Methods

The 6-month outcomes of patients with hepatotoxicity attributed to OxyELITE Pro enrolled in the DILIN prospective registry between 2004 and 2015 are presented.

Results

Six of the seven patients (86 %) presented in 2013 with symptoms of hepatitis and acute hepatocellular injury. The median duration of OxyELITE Pro use was 18 weeks (range 5–102 weeks). Median age was 36 years (range 28–62), 86 % were female, and 43 % were Asian. One patient had rash, none had eosinophilia, and three had antinuclear antibody reactivity. The median peak ALT was 2242 U/L, alkaline phosphatase 284 U/L and bilirubin 15.0 mg/dL. Six patients (86 %) were hospitalized, three developed acute liver failure and two underwent liver transplantation. DILIN causality scores for OxyELITE Pro were definite in 1, highly likely in 3, probable in 2, and possible in 1. Four of the five patients without liver transplant recovered completely within 6 months, while one patient had mild residual ALT elevations.

Conclusions

Seven cases of severe acute hepatocellular injury attributed to OxyELITE Pro are reported. These results reinforce the need to assess for HDS supplement use in patients presenting with unexplained acute hepatitis and point to the need for additional regulatory oversight of HDS products.

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Abbreviations

ALT:

Alanine aminotransferase

ANA:

Antinuclear antibody

Alk P:

Alkaline phosphatase

AST:

Aspartate aminotransferase

DILI:

Drug-induced liver injury

DILIN:

Drug-Induced Liver Injury Network

HDS:

Herbal and dietary supplement

INR:

International normalized ratio

RUCAM:

Roussel Uclaf Causality Assessment Method

ULN:

Upper limit of normal

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Funding source

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 [Indianapolis]), 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.

Authors’ contributions

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.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI, 48109-0362, USA

    Lauren A. Heidemann & Robert J. Fontana

  2. Department of Medicine, Einstein Healthcare Network, Philadelphia, PA, USA

    Victor J. Navarro

  3. Department of Medicine, Icahn School of Medicine at Mount Sinai Medical Center, New York, NY, USA

    Jawad Ahmad

  4. University of North Carolina, Chapel Hill, NC, USA

    Paul H. Hayashi

  5. University of Southern California, Los Angeles, CA, USA

    Andrew Stolz

  6. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    David E. Kleiner

Authors
  1. Lauren A. Heidemann
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  2. Victor J. Navarro
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  3. Jawad Ahmad
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  4. Paul H. Hayashi
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  5. Andrew Stolz
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  6. David E. Kleiner
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  7. Robert J. Fontana
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Corresponding author

Correspondence to Robert J. Fontana.

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Additional information

On behalf of the DILIN Investigators.

See “Appendix” section for DILIN Investigators list.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10620-016-4290-3.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 22 kb)

Appendix: DILIN Clinical Sites

Appendix: DILIN Clinical Sites

Indiana University: Naga Chalasani, MD, PI; Marwan S. Ghabril, MD, Sub-I; Raj Vuppalanchi, MD, Sub-I; [Audrey Corne, RN, EdD, Study Coord; Sherrie Cummings, RN, BSN, Study Coord; Wendy Morlan, RN, Study Coord]; University of Michigan-Ann Arbor: Robert J. Fontana, MD, PI; Hari Conjeevaram, MD, Sub-I; Frank DiPaola, MD, Sub-I; [Kristin Chesney, MBA, Study Coord; Sophana Mao, Study Coord; Cassandra Coffman, Study Coord]; University of North Carolina-Chapel Hill: Paul Watkins, MD, PI; Jama Darling, MD, Sub-I; Paul H. Hayashi, MD, Sub-I; Steven Lichtman, MD, Sub-I; Steven Zacks, MD, MPH, Sub-I; [Tracy Russell, CCRP, Study Coord; Beth Madden-Embleton, Co-Coord]; Satellite Sites: Asheville: William Harlan, MD, PI; [Tracy Russell, CCRP, Study Coord]; Wake Forest Baptist Medical Center: Herbert Bonkovsky, MD, PI; [Denise Faust, Study Coord]. University of Southern California: Andrew Stolz, MD, PI; Neil Kaplowitz, MD, Sub-I; [Susan Milstein, RN, BSN, Study Coord]; Satellite Sites: University of California-Los Angeles (Pfleger Liver Institute): Francisco A. Durazo, MD, PI; [Yolanda Melgoza, Study Coord; Val Peacock, RN, BSN, Co-Coord]; Albert Einstein Medical Center: Victor J. Navarro, MD, PI; Simona Rossi, MD, Sub-I; [Maricruz Vega, MPH, Study Coord; Manisha Verma, MD, MPH, Study Coord]; Icahn School of Medicine at Mount Sinai: Joseph Odin, MD, PhD, PI; Jawad Ahmad, MD, Co-I; Nancy Bach, Sub-I; Meena Bansal, MD, Sub-I; Charissa Chang, MD, Sub-I; Douglas Dieterich, MD, Sub-I; Priya Grewal, MD, Sub-I; Lawrence Liu, MD, Sub-I; Thomas Schiano, MD, Sub-I; [Sherif Mikhail, MD, Study Coord; Monica Taveras, Study Coord]; DILIN Data Coordinating Center at Duke Clinical Research Institute: Huiman X. Barnhart, PhD, PI; David Goldstein, PhD, Sub-I; Katherine Galan, RN, Project Lead; Alex Hammett, Lead CCRA; Cathy Wickward, CRA; Kenari Marks, CTA; Michelle McClanahan-Crowder, Data Management; Carmel Puglisi-Scharenbroich, Data Management; Hoss Rostami, Data Management; Qinghong Yang, Programmer-Statistics; Jiezhun (Sherry) Gu, PhD, Statistician; Tuan Chau, Lead Safety Associate; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): José Serrano, MD, Project Scientist; Rebecca J. Torrance, RN, MS, Clinical Trials Specialist; Rebekah Van Raaphorst, MPH, LT, USPHS, Health Research Administrator; Francisco O. Calvo, PhD, COC Contact; Jose Serrano, MD, PhD (Program Officer);Jay H. Hoofnagle, MD, Scientific Advisor; Averell H. Sherker, MD, FRCP(C), Program Officer.

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Heidemann, L.A., Navarro, V.J., Ahmad, J. et al. Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series. Dig Dis Sci 61, 2741–2748 (2016). https://doi.org/10.1007/s10620-016-4181-7

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