S5873 Ursodiol-Induced Hyperbilirubinemia in a Patient With Pre-existing Liver Disease: A Rare Adverse Outcome

Introduction: Ursodiol, a hydrophilic bile acid, is frequently prescribed for the management of primary biliary cholangitis, primary sclerosing cholangitis, and cholesterol gallstones. It enhances bile flow, reduces bile acid toxicity, and stabilizes hepatocyte membranes, thereby decreasing hepatic inflammation. Although generally well-tolerated, rare adverse effects have been reported. According to FDA labeling, post-marketing surveillance identified elevated bilirubin levels, jaundice, and hepatic enzyme abnormalities as potential adverse reactions, particularly in patients with impaired sulfation capacity. However, no definitive case reports have described this in the literature to date. We present a rare case of ursodiol-induced hyperbilirubinemia in a patient with pre-existing liver disease, underscoring the need for caution in this population. Case Description/Methods: A 77-year-old man with obesity, atrial fibrillation on apixaban, gastroesophageal reflux disease, obstructive sleep apnea, gout, and steatotic liver disease presented with abdominal pain and was diagnosed with a strangulated umbilical hernia. He underwent laparoscopic reduction and small bowel resection. During his hospital stay, he developed progressive hyperbilirubinemia after starting high-dose ursodiol for gallstone dissolution. His condition deteriorated into acute-on-chronic liver failure with multi-organ dysfunction, including cholemic nephropathy, ultimately resulting in death. Discussion: Ursodiol is widely used for its hepatoprotective properties, yet its safety in the setting of hepatic decompensation remains poorly defined. This case raises concerns about potential hepatotoxicity, especially in acutely ill patients with underlying liver disease. Post-marketing data suggest an association between high-dose ursodiol and adverse hepatic outcomes. One study linked high-dose ursodiol in early-stage primary sclerosing cholangitis with worse clinical outcomes, including liver failure and death. Although ursodiol has shown benefit in neonatal indirect hyperbilirubinemia, its role in managing hyperbilirubinemia in adults with hepatic failure is unclear. This case illustrates the need for caution when initiating ursodiol in patients with advanced liver disease and highlights the urgent need for studies evaluating its safety in this context.