S5188 A Rare Case of Hepatitis B Reactivation in a Patient Treated With Regorafenib for Gastrointestinal Stromal Tumor: A Case Report

Introduction: Regorafenib, a multikinase inhibitor approved for advanced gastrointestinal stromal tumors (GIST), is known for its hepatotoxic potential. However, hepatitis B virus (HBV) reactivation is a rarely reported complication. We present a case of HBV reactivation leading to severe hepatic injury without liver failure in a patient receiving regorafenib, compounded by concurrent Mycobacterium avium complex (MAC) infection. Case Description/Methods: A 66-year-old woman with metastatic GIST and history of breast cancer presented with weight loss and cough. Imaging revealed cavitary lung lesions, and MAC was confirmed on bronchoscopy. She was started on azithromycin, ethambutol, and rifampin. Months later, she developed jaundice and elevated liver enzymes. HBV serologies showed HBsAg positivity, anti-HBe positivity, positive anti-HBs, due to prior vaccination and high HBV DNA levels. Liver biopsy confirmed severe fibrosis (F4) with active inflammation (A3), consistent with HBV reactivation and severe hepatic injury. Tenofovir was initiated but discontinued due to Fanconi syndrome; she was transitioned to entecavir. MAC therapy was held to reduce hepatic burden. Serial monitoring showed a steady decline in viral load, HBV DNA reached minimal levels by December 2024. Liver function normalized, and the patient recovered clinically. She remains on long-term entecavir with well-controlled viremia with no recurrence of HBV. Discussion: This case highlights a rare but severe complication of regorafenib: HBV reactivation with severe hepatic injury. Tyrosine kinase inhibitors such as regorafenib may disrupt immune surveillance, leading to viral reactivation in patients with latent HBV. The coexisting MAC infection and prolonged antimicrobial therapy may have further impaired immune function. Antiviral therapy with nucleos(t)ide analogues remains the mainstay of treatment, but renal toxicity may necessitate switching agents. This case underscores the importance of routine HBV screening and prophylaxis prior to initiating immunosuppressive or targeted cancer therapies. Early identification and management of HBV reactivation are crucial to prevent life-threatening hepatic complications.