Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations?
Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations?
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DOI：
10.1111/liv.12216
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发表时间：
2013-09-01
影响因子：
6.7
通讯作者：
Verma, Sumita
中科院分区：
文献类型：
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作者：
El Sherrif, Yasser;Potts, Jonathan R.;Verma, Sumita
背景 尽管持有雄激素合成代谢类固醇 (AAS) 是非法的，但 AAS 的非处方使用仍然存在。方法 我们描述了两名白人男性（年龄分别为 25 岁和 45 岁）在摄入含有 AAS 2-17-二甲基-etiocholan-3-one,17-ol 的膳食补充剂 Mass-Drol (Celtic Dragon') 后患有胆汁淤积性肝炎的情况。结果 尽管存在大量高胆红素血症，γ-谷氨酰转移酶 (GGT) 峰值仍然正常。除了温和的小叶内胆汁淤积之外，两者的肝活检均发现小管内胞外酶表达缺陷，如 ATP8B1 疾病中所见。在老年患者中，胆盐输出泵标记（由 ABCB11 编码）局部减弱。我们假设 AAS 要么诱导了正常 ATP8B1/ABCB11 表达的抑制，要么触发了良性复发性肝内胆汁淤积 (BRIC) 1/或 2 型的初始发作。测序显示，两名患者的 ATP8B1 均正常，尽管较年轻的患者 ABCB11 中的 c.2093G>A 突变是杂合的，这是一种以前在药物诱导的多态性中遇到的情况。 肝损伤。结论 作为膳食补充剂销售的 AAS 在英国继续引起肝毒性；潜在的机制可能包括揭示遗传性胆汁淤积综合征。
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 45years) with cholestatic hepatitis following ingestion of the dietary supplement Mass-Drol (Celtic Dragon') containing the AAS 2-17-dimethyl-etiocholan-3-one,17-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.