S5866 Statins, Sartans, Semaglutide, or Stauffer’s? Dissecting Idiosyncratic Drug-Induced Hepatitis in a Complex Patient

Introduction: Drug-induced liver injury (DILI) can range from reversible hepatotoxicity to severe liver failure. While Losartan and statins are recognized for their hepatotoxic potential, semaglutide has rare reports of liver-related adverse effects. We present a case of a 54-year-old woman with severe hepatic injury that improved after cessation of losartan, rosuvastatin, and semaglutide. Case Description/Methods: A 54-year-old woman presented with acute right upper quadrant pain. Medical history included hypertension, hyperlipidemia, renal cell carcinoma (post-nephrectomy), and recent semaglutide initiation 4 weeks prior. Home medications were losartan, rosuvastatin, and semaglutide. Labs revealed alanine aminotransferase 1261 U/L, aspartate aminotransferase 1032 U/L, alkaline phosphatase 357 U/L, bilirubin 1.5 mg/dL, with worsening the next day. Workup, including hepatitis serologies, autoimmune markers, metabolic panels, and imaging, was unremarkable. Liver biopsy showed acute toxic hepatitis with mild inflammation, steatosis, and pigment deposition. Semaglutide was discontinued on admission, and Losartan was stopped on Day 2. Liver enzymes improved, and symptoms resolved. Discussion: This case exemplifies idiosyncratic drug-induced liver injury (DILI), characterized by a delayed onset, lack of alternative etiologies, and histologic confirmation. While acetaminophen toxicity is the most common cause of DILI in Western populations, idiosyncratic DILI is often linked to antibiotics and herbal supplements. Though statins and sartans are known contributors, glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide are rarely implicated. This case is unique due to the recent semaglutide initiation alongside chronic Losartan and Rosuvastatin use. Improvement after cessation of all 3 supports a drug-induced etiology. Stauffer syndrome, linked to renal cell carcinoma, was considered but deemed unlikely due to the absence of active malignancy and rapid improvement after drug withdrawal. Clinicians should consider DILI in patients presenting with unexplained liver enzyme elevations, especially with multiple potentially hepatotoxic medications. Idiosyncratic DILI requires high clinical suspicion and prompt drug cessation to prevent severe outcomes. This case highlights the need for ongoing research into the rare hepatotoxic effects of newer agents, such as semaglutide, and reinforces the importance of careful medication review in complex patients.