Fulminant Liver Failure after Treatment with a Checkpoint Inhibitor for Gastric Cancer: A Case Report and Review of the Literature

Abstract

Nivolumab is a promising monoclonal antibody inhibitor of programmed death-1, a protein on the surface of T-cells. As such, it is approved for use in patients with multiple advanced malignancies and can significantly elongate progression-free survival. However, monoclonal antibody inhibitors can lead to adverse hepatic reactions, which in rare cases result in further hepatic damage. Herein, we present a case of a patient with locally advanced gastric carcinoma treated with fluorouracil, oxaliplatin, docetaxel and the checkpoint inhibitor nivolumab. Five months after her first dosage of nivolumab and without a preexisting liver disease, she presented with transaminitis. During the course of her stay, the patient developed status epilepticus, which required mechanical ventilation followed by fulminant hepatic failure. A subsequent liver biopsy revealed severe liver damage with extensive confluent parenchymal necrosis corresponding to checkpoint-inhibitor-induced hepatitis. Alternative reasons for this hepatic failure were ruled out. Despite aggressive therapeutic interventions including corticosteroids and plasma exchange, the patient died due to liver failure. Although hepatic failure is rarely seen in patients with checkpoint inhibitor therapy, it requires early awareness and rapid intervention.

Keywords: checkpoint inhibitor; encephalitis; hepatic failure; nivolumab.

Figure 1

Timeline of the patient’s diagnosis, treatments and symptoms. Symptoms (in orange), therapy (in gray) and events (in red) are described in a timeline measured in months since diagnosis. Events are illustrated by red bars; symptoms or therapy of longer persistence are indicated by bars. FLOT: fluorouracil, oxaliplatin and docetaxel; HIPEC: hyperthermic intraperitoneal chemotherapy.

Figure 2

Representative image (diastase PAS) showing confluent and bridging necrosis with inflammatory responses (macrophages, granulocytes).