PMC6477485_01
Course after nivolumab treatment. a) Laboratory data regarding liver function and b) cytokine levels assessed by ELISAs.
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F1
Eight days after the first administration of nivolumab, he developed a high fever (39.0 C), tachycardia, appetite loss, malaise, and elevated levels of bilirubin, liver enzyme, biliary enzyme and C-reactive protein (CRP) (Table 1, Fig. 1). TCR-Gene Transduced T Cell Transfer therapy. The examination of his serum revealed marked elevation of the level of interferon (IFN)-gamma elevation in the early phase and bimodal elevation of the level of TNF-alpha (Fig. 1b). His bilirubin level decreased temporarily but subsequently increased (Fig. 1a).
Computed tomography scans of the liver on day 8. a) Non-contrast computed tomography revealed oedema of the Gleason sheath. b) Contrast computed tomography revealed neither bile duct obstruction nor liver metastasis progression.
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F2
A CT scan revealed oedema of the Gleason sheath (Fig. 2a). Neither bile duct obstruction nor liver metastasis progression was revealed (Fig. 2b). As the levels of bilirubin, biliary enzyme and CRP increased on day 9 (Fig. 2), we started prednisolone (PSL) 80 mg (1 mg/kg/day) as a treatment for nivolumab-induced liver injury and cholangitis.
H&E staining (a, b) and immunohistochemical examination (c-g) of the liver. c) Cytokeratin 7 (clone OV-TL 12/30, DAKO); d) CD3 (polyclonal antibody, DAKO); e) CD8 (clone C8/144B, DAKO); f) CD20 (clone L26, DAKO); g) CD68 (clone PG-M1, DAKO). Pathological examination revealed cholestatic liver injury and infiltration of CD8-positive T cells and macrophages into the bile duct.
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F3
Histopathological analysis of the liver revealed cholestatic liver injury (Fig. 3a). T lymphocyte and macrophage infiltration into the intrahepatic bile duct (Fig. 3b-g). There was no evidence of Epstein-Barr virus infection, cytomegalovirus infection or autoimmune disease (Table 1).