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. 2025 Sep;55(9):1285-1295.
doi: 10.1111/hepr.14224. Epub 2025 Jun 14.

Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab

Tomomitsu Matono  1 , Toshifumi Tada  2   3 , Takashi Kumada  4 , Atsushi Hiraoka  5 , Masashi Hirooka  6 , Kazuya Kariyama  7 , Joji Tani  8 , Masanori Atsukawa  9 , Koichi Takaguchi  10 , Ei Itobayashi  11 , Shinya Fukunishi  12 , Hiroki Nishikawa  13 , Kazunari Tanaka  14 , Kunihiko Tsuji  14 , Toru Ishikawa  15 , Kazuto Tajiri  16 , Yuichi Koshiyama  17 , Hidenori Toyoda  17 , Chikara Ogawa  18 , Takeshi Hatanaka  19 , Satoru Kakizaki  20 , Kazuhito Kawata  21 , Hideko Ohama  5 , Fujimasa Tada  5 , Kazuhiro Nouso  7 , Asahiro Morishita  8 , Akemi Tsutsui  10 , Takuya Nagano  10 , Norio Itokawa  9 , Tomomi Okubo  9 , Taeang Arai  9 , Takashi Nishimura  12 , Michitaka Imai  15 , Hisashi Kosaka  22 , Atsushi Naganuma  23 , Tomoko Aoki  24 , Hidekatsu Kuroda  25 , Yutaka Yata  26 , Hideyuki Tamai  27 , Takanori Matsuura  2 , Shohei Komatsu  28 , Yoshihide Ueda  29 , Yoshiko Nakamura  6 , Osamu Yoshida  6 , Shinichiro Nakamura  3 , Hirayuki Enomoto  12 , Masaki Kaibori  22 , Takumi Fukumoto  28 , Yoichi Hiasa  6 , Masatoshi Kudo  24 ; Real‐life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group
Affiliations

Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab

Tomomitsu Matono et al. Hepatol Res. 2025 Sep.

Abstract

Aim: To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre).

Methods: A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut-off values for predicting overall survival (OS).

Results: The median progression-free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7-4.4), whereas the median OS was not reached (95% CI: 12.1 months-not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second-line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230-2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033-3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months-not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months-not reached) in those with an NLR of ≥ 2.56 (p = 0.016). A Sankey diagram illustrating post-treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care (p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3-3.0 represents an appropriate cut-off for predicting OS.

Conclusions: The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.

Keywords: durvalumab; hepatocellular carcinoma; neutrophil‐to‐lymphocyte ratio; overall survival; tremelimumab.

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