Successful Treatment with Short-Term Steroid Against Severe Hepatitis Confirmed by Liver Biopsy in a Patient with Advanced Squamous-Cell Lung Cancer Receiving a Combination of Pembrolizumab, Carboplatin, and Nab-Paclitaxel: A Case Report

Anna Hayashi,1 Shinji Nakamichi,1 Yukako Nakayama,1 Atsuhiro Nagano,1 Erika Mikami,1 Natsuki Takano,1 Takehiro Tozuka,1 Masaru Matsumoto,1 Akihiko Miyanaga,1 Rintaro Noro,1 Yasuhiro Terasaki,2 Kaoru Kubota,1 Masahiro Seike,1 Akihiko Gemma1 1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Bunkyo-ku, Japan; 2Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Bunkyo-ku, JapanCorrespondence: Anna Hayashi, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Tokyo, Bunkyo-ku, 113-8603, Japan, Tel +81-3-3822-2131, Fax +81-3-5685-3075, Email k-anna@nms.ac.jpAbstract: Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets programmed death-1. Although ICIs have shown efficacy in the treatment of lung cancer, they have also been reported to cause a variety of immune-related adverse events (irAEs). Hepatotoxicity is a known irAEs, but currently, there is not enough information on its pathological characteristics and treatment. We report the case of a 70-year-old man with advanced squamous-cell lung cancer who developed severe grade 4 hepatitis on day 8 after receiving carboplatin, nab-paclitaxel, and pembrolizumab as fourth-line therapy. We treated him with steroid therapy the day after a liver biopsy was performed to investigate his pathological features, which led to a rapid and remarkable improvement. Confirmation of immune-related hepatotoxicity by pathological findings allowed the early tapering and discontinuation of steroid therapy. Performing a liver biopsy and verifying histological characteristics are needed for successful treatment with short-term steroids when drug-induced hepatitis caused by anti-cancer therapy including pembrolizumab is considered.Keywords: combination immunotherapy, immune checkpoint inhibitor, immune-related adverse events, irAEs, hepatotoxicity, liver biopsy, short-term steroid