Ohama Hideko, Hiraoka Atsushi, Tada Toshifumi, Hirooka Masashi, Kariyama Kazuya, Tani Joji, Atsukawa Masanori, Takaguchi Koichi, Itobayashi Ei, Fukunishi Shinya, Tsuji Kunihiko, Ishikawa Toru, Tajiri Kazuto, Tanaka Hironori, Toyoda Hidenori, Ogawa Chikara, Nishimura Takashi, Hatanaka Takeshi, Kakizaki Satoru, Kawata Kazuhito, Naganuma Atsushi, Kosaka Hisashi, Matono Tomomitsu, Kuroda Hidekatsu, Yata Yutaka, Nishikawa Hiroki, Imai Michitaka, Aoki Tomoko, Ochi Hironori, Tamai Hideyuki, Komatsu Shohei, Tada Fujimasa, Nakamura Shinichiro, Nakamura Yoshiko, Miyake Teruki, Yoshida Osamu, Nouso Kazuhiro, Morishita Asahiro, Itokawa Norio, Okubo Tomomi, Arai Taeang, Tsutsui Akemi, Nagano Takuya, Tanaka Kazunari, Matsuura Takanori, Koshiyama Yuichi, Kanayama Yuki, Noritake Hidenao, Enomoto Hirayuki, Matsui Kosuke, Kaibori Masaki, Fukumoto Takumi, Hiasa Yoichi, Kudo Masatoshi, Kumada Takashi
Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasuga-Machi, Matsuyama, Ehime, 790-0024, Japan.
Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
J Gastroenterol. 2025 Aug 20. doi: 10.1007/s00535-025-02290-4.
Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs.
Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed. Clinical characteristics, inflammatory markers, and nutritional indices (Geriatric Nutritional Risk Index [GNRI], body mass index, Prognostic Nutritional Index-Onodera, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio) were evaluated to identify predictors for imAE development.
The imAEs occurred in 122 patients (39.1%), most commonly affecting dermatological, gastrointestinal, and endocrine systems. On multivariate analysis, only normal GNRI (≥ 98) was independently associated with a higher incidence of imAE (odds ratio: 1.99, 95% confidence interval: 1.05-3.79, P = 0.036). Patients with GNRI ≥ 98 also showed better overall survival (OS) than those with GNRI < 98 (not reached vs. 12.5 months, P < 0.001). Among patients who developed imAEs, no significant differences were observed in the imAE types or high-dose steroid use between the GNRI ≥ 98 group (n = 66) and the GNRI < 98 group (n = 56) (40.9% vs. 58.9%, P = 0.069).
Normal GNRI status (≥ 98) was associated with an increased risk of imAE development and improved OS in patients with uHCC receiving Dur/Tre therapy. GNRI may be a useful clinical factor for identifying patients at higher risk of developing imAEs.
免疫介导的不良事件（imAEs）是不可切除肝细胞癌（uHCC）患者接受度伐利尤单抗和曲美木单抗（Dur/Tre）联合免疫治疗时的一个重大问题。本研究旨在调查与imAEs发生相关的危险因素，特别是营养和免疫标志物之间的潜在关联。
2022年11月至2024年12月期间，纳入312例接受Dur/Tre治疗的uHCC患者并进行回顾性分析。评估临床特征、炎症标志物和营养指标（老年营养风险指数[GNRI]、体重指数、预后营养指数-小野寺、C反应蛋白与白蛋白比值、中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值），以确定imAE发生的预测因素。
122例患者（39.1%）发生了imAEs，最常累及皮肤、胃肠道和内分泌系统。多因素分析显示，只有正常GNRI（≥98）与imAE的较高发生率独立相关（比值比：1.99，95%置信区间：1.05-3.79，P=0.036）。GNRI≥98的患者总体生存期（OS）也优于GNRI<98的患者（未达到与12.5个月，P<0.001）。在发生imAEs的患者中，GNRI≥98组（n=66）和GNRI<98组（n=56）之间在imAE类型或高剂量类固醇使用方面未观察到显著差异（40.9%对58.9%，P=0.069）。
正常GNRI状态（≥98）与接受Dur/Tre治疗的uHCC患者发生imAE的风险增加和OS改善相关。GNRI可能是识别发生imAEs风险较高患者的一个有用临床因素。
