1. Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations?
- Author
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Stuart Cairns, Sumita Verma, Jonathan R Potts, Adrian Barnardo, A. S. Knisely, Mark R. Howard, and Yasser El Sherrif
- Subjects
Adult ,Male ,medicine.medical_specialty ,Anabolism ,DNA Mutational Analysis ,Benign Recurrent Intrahepatic Cholestasis ,Cholestasis, Intrahepatic ,Disease ,Anabolic Agents ,Cholestasis ,Risk Factors ,Internal medicine ,medicine ,Humans ,Ingestion ,Genetic Predisposition to Disease ,ABCB11 ,ATP Binding Cassette Transporter, Subfamily B, Member 11 ,Hyperbilirubinemia ,Adenosine Triphosphatases ,Liver injury ,Hepatology ,medicine.diagnostic_test ,business.industry ,gamma-Glutamyltransferase ,Middle Aged ,medicine.disease ,Phenotype ,Endocrinology ,Liver biopsy ,Dietary Supplements ,Mutation ,Androgens ,ATP-Binding Cassette Transporters ,Chemical and Drug Induced Liver Injury ,business ,Biomarkers - Abstract
BACKGROUND: Though possession of androgenic anabolic steroids (AAS) is illegal, non-prescription use of AAS persists. METHODS: We describe two Caucasian males (aged 25 and 45 years) with cholestatic hepatitis following ingestion of the dietary supplement Mass-Drol ('Celtic Dragon') containing the AAS 2α-17α-dimethyl-etiocholan-3-one,17β-ol. RESULTS: Despite substantial hyperbilirubinaemia peak gamma-glutamyl transferase (GGT) remained normal. Besides 'bland' intralobular cholestasis, liver biopsy in both found deficiency of canalicular expression of ectoenzymes as seen in ATP8B1 disease. In the older patient, bile salt export pump marking (encoded by ABCB11) was focally diminished. We hypothesized that AAS had either induced inhibition of normal ATP8B1/ABCB11 expression or triggered initial episodes of benign recurrent intrahepatic cholestasis (BRIC) type 1/or 2. On sequencing, ATP8B1 was normal in both patients although the younger was heterozygous for the c.2093G>A mutation in ABCB11, a polymorphism previously encountered in drug-induced liver injury. CONCLUSION: AAS marketed as dietary supplements continue to cause hepatotoxicity in the UK; underlying mechanisms may include unmasking of genetic cholestatic syndromes.
- Published
- 2013