PD-L1 expressing granulomatous reaction as an on-target mechanism of steroid-refractory immune hepatotoxicity. (28th March 2019)

• Record Type: Journal Article
• Authors: Black, James RM; Goldin, Robert D; Foxton, Matthew; Marafioti, Teresa; Akarca, Ayse U; Pria, Alessia Dalla; Brock, Cathryn; Bower, Mark; Pinato, David J
• Is Part Of: Immunotherapy. Volume 11:Number 7(2019)
• Page Start: 585
• Page End: 590
• Publication Date: 2019-03-28
• Subjects: DILI -- hepatitis -- hepatotoxicity -- immune checkpoint inhibitors -- toxicity; Immunotherapy -- Periodicals; 615.37
• DOI: 10.2217/imt-2018-0187
• Languages: English
• ISSNs: 1750-743X

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.