PMC9547299_01
Pathological findings showing mild lobular hepatitis on Hematoxylin & Eosin (H&E) staining (400x) (A), differing from the findings of drug-induced liver injury. Immunohistochemical staining showing few CD138+ plasma cells. Majority of CD138+ cells were hepatocytes and bile duct epithelial cells. Only two plasma cells (arrows) are found in the lymphocyte population infiltrating the portal vein area (400x) (B). Piecemeal necrosis found in the portal vein area on H&E staining (200x) (C). Immunohistochemical staining showing more infiltrative CD4+ lymphocytes (D) than CD8+ lymphocytes (400x) (E).
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The pathological findings were mild lobular hepatitis (Fig. 1A) and small spotty-focal necrosis, which are distinct from the findings of drug-induced hepatitis (confluent lobular necrosis). A small number of plasma cells (Fig. 1B) and piecemeal necrosis was found in the portal vein area (Fig. 1C). Immunostaining showed that CD4+ lymphocytes were present in higher quantities than CD8+ lymphocytes (Fig. 1D and E).
After administration of the first course of CBDCA/PEM/pembrolizumab, an increase in blood AST and ALT levels was observed. After the second course of drug administration, AST and ALT increased again but did not decrease. We suspected irAE hepatitis, and administration of 45 mg of PSL (0.6 mg kg-1 dose-1) was started. AST and ALT levels decreased immediately after the start of PSL. The dose of PSL was decreased about every two weeks and was finally discontinued. No relapse of hepatitis was noted.. ALT: alanine aminotransferase.. AST: aspartate aminotransferase.. CBDCA: carboplatin.. PEM: pemetrexed. irAE: immune-related adverse event.. PSL: prednisolone.
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AIH. AST and ALT levels declined quickly and returned to normal on the day 111 (Fig. 2).
Chest radiography findings (A) before treatment and (B) after two courses of chemotherapy with CBDCA/PEM/pembrolizumab showing marked reduction in the primary lesion. (C) The lesion grew again after the cessation of drug therapy. (D) After two courses of chemotherapy with CBDCA/PEM, a reduction in the size of the primary lesion is observed again.. CBDCA: carboplatin, PEM: pemetrexed.
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CBDCA/PEM/pembrolizumab (Fig. 3A and B) but was increasing again due to the discontinuation of chemotherapy (Fig. 3B and C). CBDCA/PEM without pembrolizumab was restarted on the day 111 (90 days after the last administration of chemotherapy). Hepatitis was not noted, and the primary lesion shrank again (Fig. 3C and D).