Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations?

Liver Int. 2013 Sep;33(8):1266-70. doi: 10.1111/liv.12216. Epub 2013 Jun 10.

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.

Keywords: benign recurrent intrahepatic cholestasis; cholestasis; drug-induced liver injury.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics*
  • Adenosine Triphosphatases / genetics*
  • Adult
  • Anabolic Agents / adverse effects*
  • Androgens / adverse effects*
  • Biomarkers / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / genetics*
  • Cholestasis, Intrahepatic / blood
  • Cholestasis, Intrahepatic / chemically induced*
  • Cholestasis, Intrahepatic / genetics*
  • DNA Mutational Analysis
  • Dietary Supplements / adverse effects*
  • Genetic Predisposition to Disease
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Hyperbilirubinemia / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Risk Factors
  • gamma-Glutamyltransferase / blood

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Anabolic Agents
  • Androgens
  • Biomarkers
  • gamma-Glutamyltransferase
  • Adenosine Triphosphatases
  • ATP8B1 protein, human