A Case of Hepatocellular Carcinoma Successfully Resumed Atezolizumab and Bevacizumab After Associated Grade 3 Diarrhea and Grade 2 Colitis: Case Report and Literature Review

Takahiro Fuji,1 Jun Arai,1 Yumi Otoyama,1 Yuta Nio,2,3 Ikuya Sugiura,1 Yoko Nakajima,1 Atsushi Kajiwara,1 Yuki Ichikawa,1 Shojiro Uozumi,1 Yuu Shimozuma,1 Manabu Uchikoshi,1 Masashi Sakaki,1 Hisako Nozawa,1 Kenji Momo,2 Tadanori Sasaki,3 Hitoshi Yoshida1 1Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan; 2Department of Hospital Pharmaceutics, School of Pharmacy, Showa University Hospital, Tokyo, Japan; 3Department of Pharmacy, Showa University Hospital, Tokyo, JapanCorrespondence: Jun Arai, Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan, Tel +81-3-3784-8535, Fax +81-3-3784-7553, Email araiguma10@med.showa-u.ac.jpAbstract: Systemic chemotherapy has shown a significant survival benefit in patients with hepatocellular carcinoma (HCC). However, it is associated with various immune-related adverse events (irAEs). We report a case with grade 3 diarrhea and grade 2 colitis following systemic chemotherapy, successfully treated with prednisolone. An 89-year-old man was incidentally detected with a 140-mm hypervascular intrahepatic nodule on contrast-enhanced computed tomography (CECT). Washout of the contrast medium was also detected, and protein induced by vitamin K deficiency or antagonists-II (PIVKA-II) was elevated. Since the Albumin–Bilirubin (ALBI) grade was 2a without any distant metastasis, transarterial chemoembolization (TACE) was performed to treat the HCC, but several intrahepatic nodules were seen in both lobes. Therefore, the patient was treated with lenvatinib for 1 year and 4 months. A complete response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was achieved in 2 months; however, multiple hypervascular nodules were detected again. Since the ALBI grade was 1, a second round of chemotherapy with atezolizumab and bevacizumab was initiated. Although a complete response was achieved, the therapy was discontinued due to grade 3 diarrhea and grade 2 colitis after the sixth course. Based on the stool analysis and culture, CECT, and colonoscopy, the diagnosis was atezolizumab-associated colitis. Diarrhea was controlled following the oral administration of 0.5 mg/kg/day of prednisolone, and atezolizumab-bevacizumab therapy was successfully reinitiated without recurrence of colitis. The management of irAEs is important for a significant survival benefit. Systemic chemotherapy with atezolizumab and bevacizumab can be resumed despite a grade 3 irAE due to atezolizumab.Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, immune-related adverse events, ICI-mediated colitis, IL-17, PIVKA-II