S5416 De Novo Hepatocellular Carcinoma in a Heart Transplant Recipient: Rethinking the Oncogenic Risks of Tacrolimus

Introduction: Hepatocellular carcinoma (HCC) typically develops in the setting of cirrhosis, viral hepatitis, or chronic liver injury. Its appearance in solid organ transplant recipients without hepatic risk factors is rare. Tacrolimus, a calcineurin inhibitor essential for graft survival, has been linked to malignancy. This case describes incidentally discovered HCC in a heart transplant recipient on tacrolimus monotherapy, raising questions about long-term oncogenic risk. Case Description/Methods: A 75-year-old man with a history of orthotopic heart transplantation 6 years prior presented with new-onset hematochezia. He denied abdominal pain, weight loss, fatigue, or changes in appetite. He had no known history of liver disease, alcohol use, or risk factors for viral hepatitis. His only post-transplant immunosuppressive therapy was low-dose tacrolimus, with consistently stable trough levels between 4–5 ng/mL. On presentation, he was hemodynamically stable. Laboratory findings were notable for hemoglobin of 11.5 g/dL; liver enzymes and function tests were within normal limits. A contrast-enhanced computed tomography scan of the abdomen, performed to investigate the gastrointestinal bleeding, incidentally revealed a 12.1 × 9 cm hepatic mass with satellite lesions. A percutaneous biopsy confirmed moderately differentiated HCC. Serologies for hepatitis B and C were negative, and autoimmune workup was unremarkable. The patient underwent interventional embolization to address the gastrointestinal bleeding and was referred for loco-regional therapy. He remains under multidisciplinary follow-up with oncology and transplant hepatology teams. Discussion: This case highlights an unusual instance of HCC arising in the absence of usual risk factors. Although direct causation cannot be established, long-term risks tacrolimus exposure may contribute to hepatocarcinogenesis through suppression of immune surveillance and promotion of oncogenic pathways, including TGF-β signaling. The latency between transplant and tumor detection, combined with the absence of underlying liver disease, raises concern about occult oncogenic risks associated with calcineurin inhibitors. As transplant survival improves, cases like this warrant discussion around hepatic screening protocols and a potential shift toward alternative immunosuppressive regimens with anti-tumor properties, such as mTOR inhibitors. It further highlights the need for increased awareness and further study into cancer surveillance strategies for non-hepatic solid organ transplant recipients.