Anabolic-induced cholestasis: case report and literature review
DOI:
https://doi.org/10.52784/27112330.134Keywords:
cholestasis, drug-induced liver disease, liver disease, anabolic agents.Abstract
Metabolic and excretory function is determined mainly by liver activity which can make this organ susceptible to toxic injury, where dysfunction is directly or indirectly mediated by xenobiotics and/or their metabolites. Drug-induced liver disease (DILI) is a rare condition, which is associated with up to 50% of acute liver failure, and hence its importance. Direct injury can be directed to hepatocytes, bile ducts, and vascular structures, however, different xenobiotics can interfere with bile flow by directly blocking transport proteins in the canaliculi. Currently there are no definite markers for the diagnosis of this condition, and clinical manifestations can be variable, including biochemical changes in the absence of symptoms to acute liver failure and chronic liver damage, which makes it mainly an exclusion diagnosis based on clinical evidence. Scales and algorithms have been developed to assess the probability of drug, toxic, herbal, or supplement-induced liver injury. In most cases, the patient's condition typically improves when the drug responsible for the injury is removed. Although the cholestatic pattern generally has better survival rates compared to other patterns, it is also associated with a high risk of developing chronic liver disease or acting as a trigger for immune disorders in the liver. The clinical case of a patient with a cholestatic pattern of DILI due to the use of anabolic steroids is presented.
Downloads
References
Björnsson ES. Epidemiology, predisposing factors, and outcomes of drug-induced liver injury. Clin Liver Dis 2020;24:1-10. https://doi.org/10.1016/j.cld.2019.08.002.
Suh JI. Drug-induced liver injury. Yeungnam Univ J Med 2020;37:2-12. https://doi.org/10.12701/yujm.2019.00297.
Morales M L, Vélez L N, Muñoz M OG. Hepatotoxicidad: patrón colestásico inducido por fármacos. Rev Col Gastroenterol 2016;31:36-47.
Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011;53:1377-1387. https://doi.org/10.1002/hep.24229.
Andrade RJ, Lucena MI, Kaplowitz N, García-Muņoz B, Borraz Y, Pachkoria K, et al. Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry. Hepatology 2006;44:1581-1588. https://doi.org/10.1002/hep.21424.
Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 1990;11:272-276. https://doi.org/10.1016/0168-8278(90)90124-a.
Lee WM. Drug-induced hepatotoxicity. N Engl J Med 2003;349:474-485. https://doi.org/10.1056/NEJMra021844.
Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008;14:6774-6785. https://doi.org/10.3748/wjg.14.6774.
Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;46:1323-1330. https://doi.org/10.1016/0895-4356(93)90101-6.
Bhamidimarri KR, Schiff E. Drug-induced cholestasis. Clin Liver Dis 2013;17:519-531. https://doi.org/10.1016/j.cld.2013.07.015.
Yoshida EM, Erb SR, Scudamore CH, Owen DA. Severe cholestasis and jaundice secondary to an esterified testosterone, a non-C17 alkylated anabolic steroid. J Clin Gastroenterol 1994;18:268-270. https://doi.org/10.1097/00004836-199404000-00036.
Hussaini SH, Farrington EA. Idiosyncratic drug-induced liver injury: an overview. Expert Opin Drug Saf 2007;6:673-684. https://doi.org/10.1517/14740338.6.6.673.
Baumgarten R, Fengler JD, Markus R, Roschlau G, Schmehl V. [Cholestasis, hepatitis, peliosis--morphological substrate and clinical aspects of anabolic-induced liver damage]. Z Arztl Fortbild (Jena) 1983;77:519-522.
Soroka CJ, Boyer JL. Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. Mol Aspects Med 2014;37:3-14. https://doi.org/10.1016/j.mam.2013.05.001.
Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ. Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol 2005;43:342-357. https://doi.org/10.1016/j.jhep.2005.03.017.
Dawson S, Stahl S, Paul N, Barber J, Kenna JG. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab Dispos 2012;40:130-138. https://doi.org/10.1124/dmd.111.040758.
Vatakuti S, Olinga P, Pennings JLA, Groothuis GMM. Validation of precision-cut liver slices to study drug-induced cholestasis: a transcriptomics approach. Arch Toxicol 2017;91:1401-1412. https://doi.org/10.1007/s00204-016-1778-8.
Lang C, Meier Y, Stieger B, Beuers U, Lang T, Kerb R, et al. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet Genomics 2007;17:47-60. https://doi.org/10.1097/01.fpc.0000230418.28091.76.
Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, et al. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J 2003;371:361-367. https://doi.org/10.1042/bj20021886.
Köck K, Ferslew BC, Netterberg I, Yang K, Urban TJ, Swaan PW, et al. Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4. Drug Metab Dispos 2014;42:665-674. https://doi.org/10.1124/dmd.113.054304.
Mohi-ud-din R, Lewis JH. Drug- and chemical-induced cholestasis. Clin Liver Dis 2004;8:95-132. https://doi.org/10.1016/s1089-3261(03)00124-7.
Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, García-Cortes M, García-Muñoz B, et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther 2015;41:116-125. https://doi.org/10.1111/apt.13023.
Bird CE, Masters V, Clark AF. Dehydroepiandrosterone sulfate: kinetics of metabolism in normal young men and women. Clin Invest Med 1984;7:119-122.
Ramachandran R, Kakar S. Histological patterns in drug-induced liver disease. J Clin Pathol 2009;62:481-492. https://doi.org/10.1136/jcp.2008.058248.
Green RM, Crawford JM. Hepatocellular cholestasis: pathobiology and histological outcome. Semin Liver Dis 1995;15:372-389. https://doi.org/10.1055/s-2007-1007288.
Zimmerman HJ, Lewis JH. Drug-induced cholestasis. Med Toxicol Adverse Drug Exp 1987;2:112-160. https://doi.org/10.1007/BF03260010.
Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006;44:778-787. https://doi.org/10.1002/hep.21359.
Glober GA, Wilkerson JA. Biliary cirrhosis following the administration of methyltestosterone. JAMA 1968;204:170-173.
Beermann B, Ericsson JLE, Hellström K, Wengle B, Werner B. Transient cholestasis during treatment with ajmaline, and chronic xanthomatous cholestasis after administration of ajmaline, methyltestosterone and ethinylestradiol. Acta Med Scand 1971;190:241-250. https://doi.org/10.1111/j.0954-6820.1971.tb07425.x.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Hepatología’s authorship policy is based on the criteria established by the International Committee of Medical Journal Editors (ICMJE) to credit a person for their work while assigning them responsibility for its publication.
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
