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Mortality associated with the development of acute liver failure after a single dose of nivolumab



Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors are reported in all organs; however, the frequency of liver injury is low compared to irAEs in other organs. We describe a case of fulminant hepatitis after administration of the first dose of nivolumab for the management of esophageal cancer.


A man in his 80s was treated with nivolumab as a second-line therapy after his overall health worsened during preoperative chemotherapy for esophageal cancer. He was admitted to the hospital as an emergency case 30 days later with complaints of vomiting, following which acute liver failure was diagnosed.


The patient developed hepatic encephalopathy on the third day after admission and died on the seventh day. The pathological results showed sub-extensive spread hepatocellular necrosis throughout the liver, and immunostaining confirmed the presence of CD8-positive cells, which is consistent with irAEs.


Immune checkpoint inhibitors have proven to be effective for the treatment of malignant tumors, and although fatalities due to acute liver failure are extremely rare, such cases have been reported previously. Among the immune checkpoint inhibitors, anti-programmed death-1 receptor is associated with less hepatotoxicity. However, even a single dose of this treatment can cause acute liver failure, which could be fatal.

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The authors are thankful to the patients and their families for supporting the publication of this manuscript.


This study did not receive grant and funding support.

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Correspondence to Masato Yoneda.

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This work was designed by Asako Nogami from Yokohama City University Graduate School of Medicine, Department of Gastroenterology and Hepatology.

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Nogami, A., Wada, N., Muraoka, E. et al. Mortality associated with the development of acute liver failure after a single dose of nivolumab. Clin J Gastroenterol 16, 464–469 (2023).

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