Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia

doi:10.1111/apt.17906

. 2024 Apr;59(8):953-961.

doi: 10.1111/apt.17906. Epub 2024 Feb 19.

Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia

Emily Nash^{1

2}, Amanda Nicoll³, Nicholas Batt³, Jacob George^{4

5}, Varan Perananthan⁶, David Prince^{7

8}, Michael Wallace^{9

10}, Paul Gow¹¹, Karl Vaz¹¹, Shivakumar Chitturi¹², Joan Ericka Flores¹², Alicia Braund¹³, Mark Bonnichsen⁷, Stephen Riordan¹⁴, Jeremy Humphris¹⁵, Tuan Duong¹⁵, Catriona McKenzie¹⁶, Ken Liu^{1

2}, Simone I Strasser^{1

2}

Affiliations

¹ AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
² Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
³ Eastern Health, Melbourne, Victoria, Australia.
⁴ Storr Liver Centre, Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia.
⁵ University of Sydney, Sydney, New South Wales, Australia.
⁶ Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
⁷ Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia.
⁸ Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹⁰ Medical School, University of Western Australia, Perth, Western Australia, Australia.
¹¹ Austin Health, Melbourne, Victoria, Australia.
¹² The Canberra Hospital, Canberra, Australian Capital Territory, Australia.
¹³ Gold Coast University Hospital, Gold Coast, Queensland, Australia.
¹⁴ Prince of Wales Hospital, Sydney, New South Wales, Australia.
¹⁵ The Wollongong Hospital, Wollongong, New South Wales, Australia.
¹⁶ NSW Health Pathology, Sydney, New South Wales, Australia.

PMID: 38372012
DOI: 10.1111/apt.17906

Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia

Emily Nash et al. Aliment Pharmacol Ther. 2024 Apr.

. 2024 Apr;59(8):953-961.

doi: 10.1111/apt.17906. Epub 2024 Feb 19.

Authors

Affiliations

¹ AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
² Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
³ Eastern Health, Melbourne, Victoria, Australia.
⁴ Storr Liver Centre, Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia.
⁵ University of Sydney, Sydney, New South Wales, Australia.
⁶ Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
⁷ Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, New South Wales, Australia.
⁸ Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹⁰ Medical School, University of Western Australia, Perth, Western Australia, Australia.
¹¹ Austin Health, Melbourne, Victoria, Australia.
¹² The Canberra Hospital, Canberra, Australian Capital Territory, Australia.
¹³ Gold Coast University Hospital, Gold Coast, Queensland, Australia.
¹⁴ Prince of Wales Hospital, Sydney, New South Wales, Australia.
¹⁵ The Wollongong Hospital, Wollongong, New South Wales, Australia.
¹⁶ NSW Health Pathology, Sydney, New South Wales, Australia.

PMID: 38372012
DOI: 10.1111/apt.17906

Abstract

Background: Reports of DILI due to herbal and dietary supplements have been increasing over time.

Aims: To characterise clinical, laboratory and histopathological phenotypes and outcomes of drug-induced liver injury (DILI) due to anabolic-androgenic steroids (AAS), selective androgen receptor modulators (SARMs), and bodybuilding supplements (BBS) in Australia.

Methods: Retrospective case series. Patients presented to nine Australian tertiary hospitals, 2017-2023. DILI was defined biochemically and patients were included if their treating physician attributed DILI to preceding use of AAS, SARMs or BBS. Primary endpoint was time to normalisation of liver biochemistry. Secondary endpoints were hospitalisation for investigation or management of DILI, death attributable to liver injury, and liver transplantation.

Results: Twenty-three cases of DILI were identified, involving 40 drugs: 18 AAS, 14 SARMs and eight BBS. Patients were predominantly male (22/23), with median age 30 years (IQR 26-42). Most were symptomatic (21/23). Median latency of onset was 58 days (IQR 28-112 days) from drug commencement. Most patients (17/23) were admitted to hospital. Based on updated Roussel Uclaf Causality Assessment Method, DILI was possible in 17/23, probable in 2/23 and unlikely in 4/23. Median time to normalisation of liver biochemistry was 175 days (IQR 70-292 days) from presentation. Three (3/23) were treated with corticosteroids, 14/23 were treated for itch, and one (1/23) underwent liver transplantation. There were no deaths.

Conclusions: The prognosis of DILI from AAS, SARMs and BBS is good although liver transplantation may rarely be required. A detailed drug history is important in uncovering DILI due to these supplements.

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Comment in

Editorial: Muscles at the expense of liver injury. Is it worth it?
Stephens C. Stephens C. Aliment Pharmacol Ther. 2024 Apr;59(8):1003-1004. doi: 10.1111/apt.17929. Aliment Pharmacol Ther. 2024. PMID: 38523081 No abstract available.

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References

REFERENCES

1. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. Drug‐Induced Liver Injury Network. Hepatology. 2014;60:1399–1408.
1. Nash E, Sabih AH, Chetwood J, Wood G, Pandya K, Yip T, et al. Drug‐induced liver injury in Australia, 2009–2020: the increasing proportion of non‐paracetamol cases linked with herbal and dietary supplements. Med J Aust. 2021;215:261–268.
1. Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. The safety, pharmacokinetics, and effects of LGD‐4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68:87–95.
1. Machek SB, Cardaci TD, Wilburn DT, Willoughby DS. Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: a narrative review. Steroids. 2020;164:108753.
1. U.S. Food Drug Administration. FDA in brief: FDA warns against using SARMs in body‐building products. FDA; 2017. Accessed September 2023. https://www.fda.gov/news‐events/fda‐brief/fda‐brief‐fda‐warns‐against‐us...

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[1] Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. Drug‐Induced Liver Injury Network. Hepatology. 2014;60:1399–1408.

[2] Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. Drug‐Induced Liver Injury Network. Hepatology. 2014;60:1399–1408.

[3] Nash E, Sabih AH, Chetwood J, Wood G, Pandya K, Yip T, et al. Drug‐induced liver injury in Australia, 2009–2020: the increasing proportion of non‐paracetamol cases linked with herbal and dietary supplements. Med J Aust. 2021;215:261–268.

[4] Nash E, Sabih AH, Chetwood J, Wood G, Pandya K, Yip T, et al. Drug‐induced liver injury in Australia, 2009–2020: the increasing proportion of non‐paracetamol cases linked with herbal and dietary supplements. Med J Aust. 2021;215:261–268.

[5] Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. The safety, pharmacokinetics, and effects of LGD‐4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68:87–95.

[6] Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al. The safety, pharmacokinetics, and effects of LGD‐4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68:87–95.

[7] Machek SB, Cardaci TD, Wilburn DT, Willoughby DS. Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: a narrative review. Steroids. 2020;164:108753.

[8] Machek SB, Cardaci TD, Wilburn DT, Willoughby DS. Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: a narrative review. Steroids. 2020;164:108753.

[9] U.S. Food Drug Administration. FDA in brief: FDA warns against using SARMs in body‐building products. FDA; 2017. Accessed September 2023. https://www.fda.gov/news‐events/fda‐brief/fda‐brief‐fda‐warns‐against‐us...

[10] U.S. Food Drug Administration. FDA in brief: FDA warns against using SARMs in body‐building products. FDA; 2017. Accessed September 2023. https://www.fda.gov/news‐events/fda‐brief/fda‐brief‐fda‐warns‐against‐us...

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Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia

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