Abstract
Immune-related hepatitis is an important toxicity from immune-checkpoint inhibitor therapy, affecting up to 20% of patients on dual cytotoxic T-lymphocyte antigen 4/programmed cell death 1 (CTLA-4/PD-1) inhibitors. The mechanisms underlying this type of drug-induced liver injury are poorly understood. We report the case of a patient with immune-checkpoint inhibitor-related hepatitis where the presence of a diffuse granulomatous, PD-L1-positive infiltrate on liver biopsy correlated with poor response to corticosteroids. Our findings suggest a potential role for activation of the PD-1 pathway within the histiocitic infiltrate as a mechanism of toxicity. Further studies should address the role of macrophages in this patient group characterized by steroid-refractoriness.
Keywords:
DILI; hepatitis; hepatotoxicity; immune checkpoint inhibitors; toxicity.
MeSH terms
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Adrenal Cortex Hormones / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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B7-H1 Antigen / genetics
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B7-H1 Antigen / metabolism
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Biopsy
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CTLA-4 Antigen / antagonists & inhibitors
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Drug Resistance
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Drug-Related Side Effects and Adverse Reactions / diagnosis*
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Granuloma / diagnosis*
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Granuloma / etiology
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Hepatitis / diagnosis*
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Hepatitis / etiology
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Humans
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Immunotherapy / adverse effects
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Immunotherapy / methods*
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Ipilimumab / adverse effects
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Ipilimumab / therapeutic use*
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Liver / metabolism*
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Liver / pathology
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Macrophages / immunology
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Male
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Melanoma / drug therapy*
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Middle Aged
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Neoplasms, Unknown Primary / drug therapy*
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Nivolumab / adverse effects
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Nivolumab / therapeutic use*
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Programmed Cell Death 1 Receptor / antagonists & inhibitors
Substances
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Adrenal Cortex Hormones
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B7-H1 Antigen
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CD274 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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Ipilimumab
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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Nivolumab