Abstract
BackgroundNivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1 (PD-1)—have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them.MethodsEight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients.ResultsSeven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy.ConclusionsOur study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients.
Highlights
Targeted immunotherapy as a potential treatment for cancer has been intensively studied over the past decade [1, 2]
We presented eight patients who were treated with the anti-programmed cell death-1 (PD-1) agents nivolumab or pembrolizumab
Multiple patterns of liver injury were observed in these patients, including acute lobular hepatitis, steatohepatitis, and cholestatic injury
Summary
Targeted immunotherapy as a potential treatment for cancer has been intensively studied over the past decade [1, 2]. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1 antibodies) can enhance antitumor responses and delay tumor growth [9, 10]. These antibodies have shown promising results in treating several types of malignancies in recent years [2]. Methods: Eight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients. Without steroid therapy, may be sufficient in some patients
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