S2399 RAD-140: An Emerging Cause of Drug-Induced Liver Injury

Abstract

INTRODUCTION: Selective androgen receptor modulators (SARMs) include Ligandrol, enobosarm, and RAD-140. Their tissue-selective activity is thought to promote anabolic actions without significant androgenic effects. Despite lacking FDA approval, these products are widely accessible, and have been gaining popularity as alternatives to traditional androgenic anabolic steroids (AAS). Unlike AAS, only limited human hepatic safety data are available for SARMs. We report a case of drug-induced liver injury (DILI) from RAD-140. CASE DESCRIPTION/METHODS: A healthy 24-year-old Asian male presented to the emergency department with a 2-week history of diffuse abdominal pain, jaundice, scleral icterus and worsening pruritus. He did not take any prescription medications, drink alcohol, or use recreational drugs. His only over the counter medication was RAD-140, which he took for 5 weeks and stopped 2 weeks prior to the presentation due to elevated liver enzymes, noted on routine laboratory tests. Evaluation was incomplete as he left against medical advice. Three weeks later, he was hospitalized with worsening jaundice and pruritus. His mental status remained unchanged. Initial pattern of hepatocellular injury was subsequently followed by a significant cholestasis, with total bilirubin peak around the 11th week after initiating RAD-140 intake. The trend of liver tests and international normalized ratio (INR) are summarized in Table 1. Acute and chronic liver disease evaluations were all unremarkable. Despite mildly elevated alkaline phosphatase, gamma-glutamyl transpeptidase remained normal. Ferritin was significantly elevated at 1523 ng/mL but transferrin saturation was normal. Urine toxicology drug screen was also negative. Liver imaging revealed hepatomegaly and some focal fatty infiltration but excluded biliary or vascular obstruction (Figure 1, A&B). A Liver biopsy revealed blank canalicular cholestasis without remarkable inflammation consistent with drug-induced intrahepatic cholestasis (Figure 1, C&D). Currently, he remains asymptomatic with steady improvement in liver tests after being off RAD-140 for the past 5 months. DISCUSSION: Our patient represents the second reported case of significant DILI due to RAD-140, and the third case of DILI due to SARMs requiring supplement discontinuation. This case raises concerns regarding SARMs advertised selectivity and safety. Until further data is available, these agents should be used with caution.Table 1Figure 1.: A: Contrasted cross sectional imaging showing hepatomegaly and focal fatty infiltration (white arrow). B: Magnetic resonance cholangiopancreatography showing hepatomegaly and patent biliary tree. C: Liver histology showing intrahepatic cholestasis (black arrow). D: Liver histology showing minimal portal inflammation (black arrow).