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

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.

Keywords: drug-induced hepatitis; drug-induced liver injury (dili); hepatotoxic agent; hepatotoxic drugs; selective androgen receptor modulators.

Figure 1. Liver biopsy (hematoxylin and eosin, 20x).

The image is showing lymphocytic infiltration within the portal area (encircled).

Figure 2. Liver biopsy (hematoxylin and eosin, 20x).

The image is showing lobular cholestasis (arrowheads).

Figure 3. Liver biopsy (hematoxylin and eosin, 20x).

The image is showing ceroid-laden macrophages (arrows).

Figure 4. Alkaline phosphatase (ALP) and transaminases trend.

Graph showing ALP and transaminases trend over 35 days. AST: aspartate transaminase; Alk P: alkaline phosphatase

Figure 5. Direct and total bilirubin trend.

Graph showing direct and total bilirubin trend. We notice that total bilirubin peaked at 31 and down trended to 11 at 35 days. T. bill: total bilirubin