Liver injury after the use of anabolic steroids to promote muscle growth – single-center experience

Czech version

Authors: P. Molčan ¹; T. Koller ²; N. Bystrianska ¹; J. Strachan ¹; D. Janceková ¹; J. Vnenčáková ¹; P. Vrbová ²; P. Strenáčik ¹; L. Skladaný ¹
Authors‘ workplace: HEGITO – hepatologické, gastroenterologické a transplantačné oddelenie, II. interná klinika SZU a FNsP F. D. Roosevelta Banská Bystrica ¹; Gastroenterologické a hepatologické oddelenie, V. interná klinika LF UK a UN Bratislava-Ružinov ²
Published in: Gastroent Hepatol 2021; 75(2): 118-124
Category:
doi: https://doi.org/10.48095/ccgh2021118

Overview

Introduction: Anabolic agents are prohibited in professional sports, but their availability makes its use widespread among amateur athletes. Our goal was to report all cases of anabolic-induced liver injury. Patients and methods: We included all inpatients with acute liver injury and previous anabolic use over the last 4 years. We recorded history, demographics, laboratory data and imaging, histology, HPVG (hepatic venous pressure gradient) and the outcome. Results: Fifteen men with a median age of 33.1 years were identified. Common symptoms were dyspepsia (47%), jaundice (100%) and dark urine (26.7%); anabolics were used for a median of 66.5 days (25^th–75^th percentile, 18.3–113.5), baseline bilirubin level was 19.4-times higher than the upper limit of the normal (13.9–27.1), 1 patient (6.7%) had INR > 1.7. The character of the injury was cytolytic in 3 patients (20%), and cholestatic and mixed in 6 patients (40%). Significant alcohol consumption was reported in 2 cases and 4 (26.7%) patients had hepatic steatosis. Patients consuming alcohol had higher baseline and maximum bilirubin level (367 vs. 731 and 454 vs. 801 μmol/ L, P < 0.05). All 10 patients with liver biopsy demonstrated cholestasis, the interface hepatitis in 5 patients (50%), one had F1 fibrosis. The median HVPG was 5 mmHg (4–6). All patients were treated with sylimarin, ACC and UDCA, two (13.3%) with steroids, three (20%) required MARS. The median time to normalize bilirubin was 99 days (64.3–113.5), no death was observed. Conclusion: Experience with anabolic-induced liver injury shows that they lead to cholestatic injury requiring hospitalization and slow recovery with significant costs. Alcohol consumption and steatosis might have a cumulative effect.

Conflict of Interest: The authors declare that the article/ manuscript complies with ethical standards, patient anonymity has been respected, and they state that they have no
fi nancial, advisory or other commercial interests in relation to the subject matter.
Publication Ethics: This article/ manuscript has not been published or is currently being submitted for another review. The authors agree to publish their name and e-mail in
the published article/ manuscript.
Dedication: The article/ manuscript is not supported by a grant nor has it been created with the support of any company.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for bio medical papers.

Keywords:

drug-induced liver injury – anabolics – Prognosis – Steatosis

Sources

Bagatell CJ, Bremner WJ. Androgens in men – uses and abuses. New Engl J Med 1996; 334(11): 707–714. doi: 10.1056/ NEJM199603143341107.
Cruz-Jentoft AJ, Bahat G, Bauer J et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019; 48(1): 16–31. doi: 10.1093/ ageing/ afy169.
Fontana RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology 2014; 146(4): 914–928. doi: 10.1053/ j.gastro.2013.12.032.
Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther 2015; 41(1): 116–125. doi: 10.1111/ apt.13023.
Nieschlag E, Vorona E. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol 2015; 173(2): R47–R58. doi: 10.1530/ EJE-15-0080.
Rowe R, Berger I, Copeland J. “No pain, no gainz”? Performance and image-enhancing drugs, health effects and information seeking. Drugs Educ Prev Policy 2017; 24(5): 400–408. doi: 10.1080/ 09687637.2016.1207752.
Ip EJ, Barnett MJ, Tenerowicz MJ et al. The Anabolic 500 survey: characteristics of male users versus nonusers of anabolic-androgenic steroids for strength training. Pharmacotherapy 2011; 31(8): 757–766. doi: 10.1592/ phco.31.8.757.
Kimergård A. A qualitative study of anabolic steroid use amongst gym users in the United Kingdom: motives, beliefs and experiences. J Subst Use 2015; 20(4): 288–294. doi: 10.3109/ 14659891.2014.911977.
Sagoe D, Andreassen CS, Pallesen S. The aetiology and trajectory of anabolic-androgenic steroid use initiation: a systematic review and synthesis of qualitative research. Subst Abuse Treat Prev Policy 2014; 9: 27. doi: 10.1186/ 17 47-597X-9-27.
Díaz FC, Sáez-González E, Benlloch S et al. Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis. Ann Hepatol 2016; 15(6): 939–943. doi: 10.5604/ 16652681.1222114.
Mikas J. Informácia o výskyte škodlivého výrobku – výživový doplnok obsahujúci anabolické steroidy. 2020 [online]. Available from: https:/ / www.uvzsr.sk/ index.php?option=com_content&view=article&id=4248:informacia-o-vyskyte-kodliveho-vyrobku-vyivovy-doplnok-obsahujuci-anabolicke-steroidy&catid=95:informacie-pre-spotrebiteov.
Krishnan PV, Feng ZZ, Gordon SC. Prolonged intrahepatic cholestasis and renal failure secondary to anabolic androgenic steroid-enriched dietary supplements. J Clin Gastroenterol 2009; 43(7): 672–675. doi: 10.1097/ MCG.0b013e318188be6d.
Kafrouni MI, Anders RA, Verma S. Hepatotoxicity associated with dietary supplements containing anabolic steroids. Clin Gastroenterol Hepatol 2007; 5(7): 809–812. doi: 10.1016/ j.cgh.2007.02.036.
Shah NL, Zacharias I, Khettry U et al. Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases. Clin Gastroenterol Hepatol 2008; 6(2): 255–258. doi: 10.1016/ j.cgh.2007.11.010.
Sanyal AJ, Bosch J, Blei A, et al. Portal hypertension and its complications. Gastroenterology 2008; 134(6): 1715–1728. doi: 10.1053/ j.gastro.2008.03.007.
Burroughs AK, McCormick PA. Natural history and prognosis of variceal bleeding. Baillieres Clin Gastroenterol 1992; 6(3): 437–450. doi: 10.1016/ 0950-3528(92)90031-9.
Krook H. Estimation of portal venous pressure by occlusive hepatic vein catheterization. Scand J Clin Lab Invest 1953; 5(3): 285–292. doi: 10.3109/ 00365515309094199.
La Mura V, Nicolini A, Tosetti G et al. Cirrhosis and portal hypertension: the importance of risk stratification, the role of hepatic venous pressure gradient measurement. World J Hepatol 2015; 7(4): 688–695. doi: 10.4254/ wjh.v7.i4.688.
Lebrec D, Nouel O, Bernuau J et al. Portal hypertension in fulminant viral hepatitis. Gut 1980; 21(11): 962–964. doi: 10.1136/ gut.21.11.962.
Navasa M, Garcia-Pagán JC, Bosch J et al. Portal hypertension in acute liver failure. Gut 1992; 33(7): 965–968. doi: 10.1136/ gut.33.7.965.
Lebrec D, Benhamou JP. Noncirrhotic intrahepatic portal hypertension. Semin Liver Dis 1986; 6(4): 332–340. doi: 10.1055/ s-2008-1040615.
Schröder T, Schmidt KJ, Olsen V et al. Liver steatosis is a risk factor for hepatotoxicity in patients with inflammatory bowel disease under immunosuppressive treatment. Eur J Gastroenterol Hepatol 2015; 27(6): 698–704. doi: 10.1097/ MEG.0000000000000350.
Liu LW, Zhao XY, Jia JD. EASL clinical practice guidelines recommendations for drug-induced liver injury in 2019. Zhonghua Gan Zang Bing Za Zhi 2019; 27(6): 420–423. doi: 10.3760/ cma.j.issn.1007-3418.2019.06.006.
Gillessen A, Schmidt HH. Silymarin as supportive treatment in liver diseases: a narrative review. Adv Ther 2020; 37(4): 1279–1301. doi: 10.1007/ s12325-020-01251-y.
de Andrade KQ, Moura FA, dos Santos JM et al. Oxidative stress and inflammation in hepatic diseases: therapeutic possibilities of N-Acetylcysteine. Int J Mol Sci 2015; 16(12): 30269–30308. doi: 10.3390/ ijms161226225.
Brůha R. Hepatoprotektiva. Klin Farmakol Farm 2006; 20(3): 154–157.
Katsinelos P, Vasiliadis T, Xiarchos P et al. Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin)-induced intra-hepatic cholestasis: report of two cases. Eur J Gastroenterol Hepatol 2000; 12(3): 365–368. doi: 10.1097/ 00042737-200012030-00017.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu;European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67(1): 145–172. doi: 10.1016/ j.jhep.2017.03.022.