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Histologic patterns of liver injury induced by anti-PD-1 therapy
Dongwei Zhang, John Hart, Xianzhong Ding, Xuchen Zhang, Michael Feely, Lindsay Yassan, Lindsay Alpert, Consuelo Soldevila-Pico, Xuefeng Zhang, Xiuli Liu ... Show more
Gastroenterology Report, goz044, https://doi.org/10.1093/gastro/goz044
Published:
20 September 2019
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Abstract
Background
Nivolumab 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.
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.
Results
Seven 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.
Conclusions
Our 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.
nivolumab, pembrolizumab, anti-PD-1, liver injury, histology, hepatitis
Topic:
liver injuries autoimmune hepatitis cholestasis hepatitis liver function steatohepatitis, non-alcoholic hepatotoxicity cancer, advanced nivolumab pembrolizumab
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Original Article |
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发表于 2019-9-25 16:07
