Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids.
BACKGROUND
We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.


OBJECTIVE
To characterise phenotype presentation, outcome and severity of AAS DILI.


METHODS
Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases.


RESULTS
AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.


CONCLUSIONS
Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
Servicio de Farmacología Clínica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
M
M
Robles-Diaz
A
A
Gonzalez-Jimenez
I
I
Medina-Caliz
C
C
Stephens
M
M
García-Cortes
B
B
García-Muñoz
A
A
Ortega-Alonso
E
E
Blanco-Reina
R
R
Gonzalez-Grande
M
M
Jimenez-Perez
P
P
Rendón
J M
JM
Navarro
P
P
Gines
M
M
Prieto
M
M
Garcia-Eliz
F
F
Bessone
J R
JR
Brahm
R
R
Paraná
M I
MI
Lucena
R J
RJ
Andrade
D058186:Acute Kidney Injury / Q000209:etiology; D000328:Adult; D000368:Aged; D045930:Anabolic Agents / Q000009:adverse effects*; D000728:Androgens / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000503:physiopathology*; D002779:Cholestasis / Q000150:complications; D003404:Creatinine / Q000097:blood; D006801:Humans; D007565:Jaundice / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D055815:Young Adult
D045930:Anabolic Agents; D000728:Androgens; D003404:Creatinine; D001663:Bilirubin