Drug-induced liver injury

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paractamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature, since affected individuals represent only a small proportion of those treated with such drugs. In many cases the mechanism for idiosyncrasy is immune mediation and is often identified by genetic risk determined by HLA variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, though recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued especially in the presence of elevated transaminases (AST/ALT ≥5ULN) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory

Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149370/1/apt15211_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149370/2/apt15211.pd

Phenotype of hepatocellular neoplasms associated with androgen use

A

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

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

Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health

Twenty-four products suspected of containing anabolic steroids and sold in fitness equipment shops in the United Kingdom (UK) were analyzed for their qualitative and semi-quantitative content using full scan gas chromatography-mass spectrometry (GC-MS), accurate mass liquid chromatography-mass spectrometry (LC-MS), high pressure liquid chromatography with diode array detection (HPLC-DAD), UV-Vis, and nuclear magnetic resonance (NMR) spectroscopy. In addition, X-ray crystallography enabled the identification of one of the compounds, where reference standard was not available. Of the 24 products tested, 23 contained steroids including known anabolic agents; 16 of these contained steroids that were different to those indicated on the packaging and one product contained no steroid at all. Overall, 13 different steroids were identified; 12 of these are controlled in the UK under the Misuse of Drugs Act 1971. Several of the products contained steroids that may be considered to have considerable pharmacological activity, based on their chemical structures and the amounts present. This could unwittingly expose users to a significant risk to their health, which is of particular concern for naïve users