Nivolumab-induced hepatitis: A rare side effect of an immune check point inhibitor

Abstract

Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.

Acute Liver Failure following a Single Dose of Atezolizumab, as Assessed for Causality Using the Updated RUCAM

“…To our knowledge, this is the first documented report of a patient developing acute liver failure shortly after ICI initiation. A single case of nivolumab-induced hepatitis in a patient with renal cell carcinoma which developed within two weeks of therapy initiation was previously reported but was not as clinically severe [ 16 ].…”

Cycle-dependent eosinophilia due to adjuvant nivolumab for malignant melanoma

“…1,3 However, this alteration in the activity of the T-cells can cause them to lose their ability to identify host cells and lead to immune-related adverse events, including dermatitis, thyroid dysfunction, hepatitis, pneumonitis, hypophysitis, enteritis, nephritis, and rarely, hematologic effects. 3,4…”

“…Nivolumab is a PD-1 ICI antibody that disrupts the interaction of the PD-1 receptor with its ligands PDL-1 and PDL-2, thereby enhancing antitumor immunity, delaying tumor progression, and facilitating tumor rejection. 1,3 However, this alteration in the activity of the T-cells can cause them to lose their ability to identify host cells and lead to immune-related adverse events, including dermatitis, thyroid dysfunction, hepatitis, pneumonitis, hypophysitis, enteritis, nephritis, and rarely, hematologic effects. 3,4 The cytokine interleukin-2 (IL-2) is an essential growth factor for T-cells.…”

Treatment of patients with cancer using PD‑1/PD‑L1 antibodies: Adverse effects and management strategies (Review)

“…The management strategy for this side effect was administration of steroids and the patient began to exhibit improvements in liver function. However, she later developed substantial upper gastrointestinal bleeding secondary to a gastroduodenal ulcer and then developed acute tubular necrosis, ultimately succumbing to the complications ( 59 ). Lankes et al ( 60 ) reported severe diarrhea with ≤18 watery bowel movements per day in a patient with metastatic melanoma treated with ipilimumab.…”