Liver transplantation in a patient with metastatic hepatocellular carcinoma after downstaging with single-agent immunotherapy: the first case report.

Background: Immunotherapy in hepatocellular carcinoma (HCC) has changed the clinical practice for unresectable and advanced setting after the approvals of atezolizumab plus bevacizumab and durvalumab plus tremelimumab (STRIDE regimen). A growing field for its application is the use of systemic therapy to achieve disease control in patients already listed for liver transplantation (LT) (bridging therapy) and fitting those not eligible within the LT criteria (conversion therapy). However, there is still a lack of prospective data for using immune checkpoint regimens in this setting, especially regarding the treatment-free interval before LT which may be different based on the immunotherapy drug chosen. Here, we present the first case in the literature of a patient with metastatic extrahepatic disease [Barcelona Clinic Liver Cancer (BCLC)-C] and severe alcoholic cirrhosis who successfully LT after a prolonged radiologic complete response (CR) to single-agent immunotherapy. Case Description: A 61-year-old man with a diagnosis of advanced hepatocellular carcinoma (aHCC) (abdominal lymph nodes, lung, mediastinal nodes, bone) in the setting of alcoholic cirrhosis with a history of esophageal varices was treated with single-agent nivolumab 480 mg intravenous (IV) every four weeks for approximately 17 months (18 cycles) with partial response (PR). Considering the prolonged disease control, systemic therapy was discontinued. Three months after the treatment stopped, a new hepatic lesion was detected on abdominal magnetic resonance imaging (MRI). The new hepatic lesion was treated with microwave ablation (MWA) with a CR. After 10 months from MWA, the patient was free of active disease in the context of a slow, delayed response to immunotherapy. With the aim to treat his underlying liver disease, the patient received orthotopic LT, and he is currently free of cancer after one year of follow-up. Conclusions: LT in patients with aHCC with CR to immunotherapy may be feasible and safe in carefully selected patients, potentially curing the underlying liver disease, which impacts both survival and quality of life. However, the immunosuppressive state induced by LT may facilitate the disease progression of extrahepatic disease, therefore this should be considered only in selected patients with a prolonged CR to systemic therapy.