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World J Gastroenterol. Jul 14, 2022; 28(26): 3071-3080
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3071
Anabolic androgenic steroid-induced liver injury: An update
Ana Petrovic, Sonja Vukadin, Renata Sikora, Kristina Bojanic, Robert Smolic, Davor Plavec, George Y Wu, Martina Smolic
Ana Petrovic, Sonja Vukadin, Robert Smolic, Martina Smolic, Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Ana Petrovic, Sonja Vukadin, Martina Smolic, Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Renata Sikora, Department of Dental Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Renata Sikora, Department of Dental Medicine, Health Center Osijek-Baranja County, Osijek 31000, Croatia
Kristina Bojanic, Department of Otorhinolaryngology, Neurosurgery and Radiology, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Kristina Bojanic, Department of Biophysics and Radiology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Kristina Bojanic, Department of Radiology, Health Center Osijek-Baranja County, Osijek 31000, Croatia
Davor Plavec, Research Department, Srebrnjak Children's Hospital, Zagreb 10000, Croatia
George Y Wu, Department of Medicine, Division of Gastrenterology/Hepatology, University of Connecticut Health Center, Farmington, CT 06030, United States
Author contributions: Petrovic A, Smolic R, Smolic M, and Wu GY designed the research study; Petrovic A, Vukadin S, Sikora R, Bojanic K, Plavec D, and Smolic M performed the research; Petrovic A and Vukadin S analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Martina Smolic, MD, PhD, Professor, Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 10E Cara Hadrijana, Osijek 31000, Croatia. martina.smolic@mefos.hr
Received: January 11, 2022
Peer-review started: January 11, 2022
First decision: March 8, 2022
Revised: March 22, 2022
Accepted: June 18, 2022
Article in press: June 18, 2022
Published online: July 14, 2022
Processing time: 182 Days and 12.4 Hours
Abstract

Anabolic androgenic steroids (AASs) are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects. These properties make them therapeutically beneficial in medical conditions such as hypogonadism. However, they are commonly bought illegally and misused for their anabolic, skeletal muscle building, and performance-enhancing effects. Supraphysiologic and long-term use of AASs affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders. Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse. Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis, peliosis hepatis, and hepatic benign and malignant tumors. It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors, upregulation of bile acid synthesis, and induction of hepatocyte hyperplasia. Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS. However, some long-term consequences are irreversible. AAS-induced liver injury should be taken in consideration in patients with liver disorders, especially with the increasing unintentional ingestion of supplements containing AAS. In this paper, we review the most current knowledge about AAS-associated adverse effects on the liver, and their clinical presentations, prevalence, and pathophysiological mechanisms.

Keywords: Androgens; Steroids; Cholestasis; Fibrosis; Liver; Chemical and drug induced liver injury

Core Tip: There is a great deal of literature on the prevalence, pathophysiology, and therapeutic options for anabolic androgenic steroid (AAS)-associated adverse effects. However, AAS-induced liver injury is perhaps still underreported and poorly understood. In this paper, we review the latest knowledge obtained about molecular mechanisms of AAS-associated liver injury from most recent in vitro and animal studies, as well as the latest case reports regarding adverse effects of AASs in dietary supplements.