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Liver Transplantation Following Hepatocellular Carcinoma Rupture and Long-Term Immunotherapy: A Case Report
Lorenza Di Marco1, Marco Scoppettuolo2, Alessandra Pivetti2
1Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena, 41124, Italy. lor.dimarco@gmail.com.
Aim:
To report a case of advanced hepatocellular carcinoma (HCC) complicated by tumor rupture, successfully downstaged with combined oncolytic immunotherapy (Pexa-Vec) and a PD-1 inhibitor (Nivolumab), ultimately enabling liver transplantation (LT). This report highlights the potential role of immune checkpoint inhibitors (ICIs) as bridging therapy in otherwise ineligible patients.
Methods:
A 54-year-old male with HCV-related cirrhosis presented with multifocal, unresectable HCC (BCLC C) complicated by hemoperitoneum. Surgery was not indicated. He was enrolled in a Phase I/IIa trial of intralesional Pexa-Vec and intravenous Nivolumab (240 mg every 14 days). Percutaneous biopsies confirmed Edmondson-Steiner grade 2 HCC. Clinical, laboratory, and imaging follow-up were performed throughout therapy. Pre-transplant screening was performed after 4 years of stable disease.
Results:
The patient received three intralesional Pexa-Vec injections and 93 cycles of Nivolumab over four years, with only mild, transient adverse events. Imaging showed stable disease without extrahepatic spread. Pre-LT evaluation confirmed preserved liver function (Child-Pugh A5, ECOG 0). Immunotherapy was suspended 12 weeks before LT, and LT was performed successfully in September 2023. Post-transplant follow-up (24 months) revealed no recurrence of HCC or graft rejection. HCV was eradicated with direct-acting antivirals. Explant pathology showed complete necrosis in injected nodules and regressive changes in other lesions.
Conclusions:
ICIs alone or in combination with oncolytic immunotherapy may serve as novel downstaging strategies in advanced, ruptured HCC. Successful LT with long-term disease-free survival challenges traditional concerns about peritoneal seeding. Larger studies are required to define optimal patient selection, timing, and safety of pre-transplant ICIs. A 54-year-old man with advanced, ruptured liver cancer had an unexpectedly stable course over four years while receiving immunotherapy and an oncolytic virus. He later underwent a liver transplant and remains cancer-free two years later, illustrating the unpredictable nature of some severe liver cancer cases.
Clinical Trial Registration:
Not applicable.
