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选择性雄激素受体调节剂(SARMs)所致肝损伤:一例报告及文献复习

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature.

作者信息

Mohamed Wael T, Jahagirdar Vinay, Fatima Ifrah, Ahmed Mohamed K, Jaber Fouad, Wang Kevin, Hassan Amira, Ewing Eric, Clarkston Wendell, Likhitsup Alisa

机构信息

Internal Medicine, University of Missouri Kansas City, Kansas City, USA.

Pathology, University of Missouri Kansas City, Kansas City, USA.

出版信息

Cureus. 2023 Feb 17;15(2):e35094. doi: 10.7759/cureus.35094. eCollection 2023 Feb.

Abstract

Drug-induced liver injury (DILI) is one of the leading causes of death from acute liver failure (ALF) in the United States, accounting for approximately 13% of ALF cases in the United States. Selective androgen receptor modulators (SARMs) were first developed to increase muscle mass while avoiding the side effects of conventional androgenic steroids. Although not Food and Drug Administration (FDA) approved, they are widely available online and are consumed to enhance athletic performance. We report a 22-year-old, previously healthy male, who presented with a two-week history of worsening jaundice, nausea, fatigue, pruritus, dark urine, and light stools. He reported taking the SARM, RAD-140, for 16 weeks. Examination showed scleral icterus. The liver panel showed alkaline phosphatase (ALP) 5.3 µkat/L, alanine transaminase (ALT) 1.66 µkat/L, aspartate transaminase (AST) 1.18 µkat/L, direct bilirubin 294 µmol/L, total bilirubin 427.5 µmol/L, and international normalized ratio (INR) 0.9. Viral hepatitis and autoimmune panel were unremarkable. Alpha-1 antitrypsin and ceruloplasmin levels were within normal limits. Bile sludge was seen on ultrasound. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed segmental narrowing of the intrahepatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. Liver biopsy showed mixed portal hepatitis, cholestasis, and biliary reactive changes with ceroid-loaded macrophages; a picture consistent with DILI. The patient was treated supportively and discharged with scheduled hepatology follow-up. At the one-month follow-up, his total bilirubin had fallen from a peak of 530 mol/L to 188 mol/L. The diagnosis of DILI can be made based on the timing of exposure and the exclusion of other etiologies. Liver enzymes normalized three to 12 months after product discontinuation. We hope this report will remind primary care physicians of the potential hepatotoxic side effects of muscle-building compounds and encourage them to report suspected DILI to the FDA using the MedWatch system.

摘要

药物性肝损伤(DILI)是美国急性肝衰竭(ALF)致死的主要原因之一,约占美国ALF病例的13%。选择性雄激素受体调节剂(SARMs)最初是为增加肌肉量同时避免传统雄激素类类固醇的副作用而研发的。尽管未获美国食品药品监督管理局(FDA)批准,但它们在网上广泛可得,且被用于提高运动表现。我们报告一例22岁既往健康男性,出现黄疸加重、恶心、乏力、瘙痒、尿色加深及粪便变浅2周病史。他自述服用SARM类药物RAD - 140达16周。检查发现巩膜黄染。肝功能检查显示碱性磷酸酶(ALP)5.3微卡特/升,丙氨酸转氨酶(ALT)1.66微卡特/升,天冬氨酸转氨酶(AST)1.18微卡特/升,直接胆红素294微摩尔/升,总胆红素427.5微摩尔/升,国际标准化比值(INR)0.9。病毒性肝炎及自身免疫指标无异常。α1抗胰蛋白酶及铜蓝蛋白水平在正常范围内。超声检查发现胆汁淤积。腹部磁共振胰胆管造影(MRCP)显示肝内胆管节段性狭窄。内镜逆行胰胆管造影(ERCP)无异常。肝活检显示混合性门脉性肝炎、胆汁淤积及胆管反应性改变伴含蜡样质的巨噬细胞;符合DILI表现。患者接受支持治疗并出院,安排了肝病随访。在1个月随访时,其总胆红素已从峰值530微摩尔/升降至188微摩尔/升。DILI的诊断可基于接触时间及排除其他病因做出。停用相关产品后3至12个月肝酶恢复正常。我们希望本报告能提醒基层医疗医生注意增肌化合物潜在的肝毒性副作用,并鼓励他们使用MedWatch系统向FDA报告疑似DILI病例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1bf/10024817/b993704d8695/cureus-0015-00000035094-i01.jpg

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