S5500 Beyond the Label: Hepatotoxicity Following the Use of a Testosterone-Boosting Supplement

Introduction: Twenty percent of all drug induced liver injuries (DILI) occur secondary to herbal supplements. Diagnosis can be challenging due to the lack of regulation, improper labeling, and inconsistent ingredient concentrations. Product inconsistency leads to varying clinical presentations and severity of liver injury, ultimately delaying diagnosis and treatment. Case Description/Methods: The patient is a 70-year-old man who presented with abdominal pain and fatigue. Labs were notable for an aspartate aminotransferase (AST) of 1,472, alanine aminotransferase (ALT) of 1,315, total bilirubin (tbili) of 2.3, alkaline phosphatase of 1,200, Hgb of 18.7, ferritin of 37,000, and percent iron saturation of 94. He endorsed recent initiation of a supplement marked as a testosterone booster that utilizes ashwagandha, Eurycoma longifolia and ginseng. He also endorsed drinking 2 cups of vodka per day. Initial differential included hemophagocytic lymphohistiocytosis (HLH), hereditary hemochromatosis (HH), underlying infiltrative disease, malignancy, and DILI. MRCP showed iron deposits in the liver, but a trial of deferoxamine infusions did not yield improvement. Labs peaked with an AST of 2,939, ALT of 1,945, tbili of 34, ferritin of 66,000, international normalized ratio of 1.1, and ammonia of 105. Liver biopsy demonstrated acute and chronic hepatitis with hepatocyte ballooning and necrosis, findings consistent with DILI. The previously mentioned supplement was implicated as the most likely cause and he was started on prednisone 30 mg/day. He developed subsequent improvement in liver function tests (LFT) with an AST of 131, ALT of 204, alkaline phosphatase of 159, and tbili of 10.9. Discussion: As in our patient, the degree of LFT abnormality may be profound and masquerade as other diagnoses. Our initial differential included HH and HLH, both of which can present with elevated ferritin, hepatic involvement, and a subsequent rise in LFTs. Additionally, there have been cases of DILI that masked underlying HH, further complicating the clinical picture. This patient’s possible underlying HH likely augmented the severity of DILI secondary to ashwagandha. Underlying liver disease is associated with both a higher likelihood of DILI and worse outcomes. Our patient did not ultimately develop liver failure. However, there are case reports of DILI secondary to herbal/dietary supplements resulting in need for liver transplant, especially in patients with preexisting liver disease. This emphasizes the need for recognizing the role herbal supplements play in DILI, allowing for earlier diagnosis and treatment.