Association of Metabolic-Associated Steatotic Liver Disease With Clinical Outcomes of Durvalumab and Tremelimumab in Advanced Hepatocellular Carcinoma Patients: A Multicenter Study

Takeshi Hatanaka; Shigeo Shimose; Takanori Ito; Joji Tani; Tetsu Tomonari; Issei Saeki; Yasuto Takeuchi; Kyo Sasaki; Yuichi Honma; Ryu Sasaki; Naoki Yoshioka; Takehito Naito; Mamiko Takeuchi; Tetsuya Yasunaka; Masahiro Sakata; Hideki Iwamoto; Satoshi Itano; Yuki Kanayama; Tomotake Shirono; Norikazu Tanabe; Takafumi Yamamoto; Atsushi Naganuma; Sohji Nishina; Motoyuki Otsuka; Hideki Kobara; Taro Takami; Tetsuji Takayama; Takumi Kawaguchi; Hiroki Kawashima; Masaru Harada; Hisamitsu Miyaaki; Satoru Kakizaki; Hepatology InVestigator Experts in Japan (HIVE‐J) Study Group

doi:10.1111/hepr.70023

Association of Metabolic-Associated Steatotic Liver Disease With Clinical Outcomes of Durvalumab and Tremelimumab in Advanced Hepatocellular Carcinoma Patients: A Multicenter Study

Hepatol Res. 2025 Dec;55(12):1642-1651. doi: 10.1111/hepr.70023. Epub 2025 Aug 21.

Authors

Takeshi Hatanaka¹, Shigeo Shimose², Takanori Ito³, Joji Tani⁴, Tetsu Tomonari⁵, Issei Saeki⁶, Yasuto Takeuchi⁷, Kyo Sasaki⁸, Yuichi Honma⁹, Ryu Sasaki¹⁰, Naoki Yoshioka¹¹, Takehito Naito¹², Mamiko Takeuchi¹³, Tetsuya Yasunaka¹⁴, Masahiro Sakata¹⁵, Hideki Iwamoto^{2

16}, Satoshi Itano¹⁷, Yuki Kanayama¹, Tomotake Shirono², Norikazu Tanabe⁶, Takafumi Yamamoto¹², Atsushi Naganuma¹⁸, Sohji Nishina⁸, Motoyuki Otsuka⁷, Hideki Kobara⁴, Taro Takami⁶, Tetsuji Takayama⁵, Takumi Kawaguchi², Hiroki Kawashima³, Masaru Harada⁹, Hisamitsu Miyaaki¹⁰, Satoru Kakizaki¹⁹; Hepatology InVestigator Experts in Japan (HIVE‐J) Study Group

Affiliations

¹ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
² Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
³ Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
⁵ Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, Tokushima, Japan.
⁶ Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
⁷ Department of Gastroenterology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Japan.
⁹ Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
¹⁰ Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹¹ Department of Gastroenterology and Hepatology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
¹² Department of Gastroenterology, Toyohashi Municipal Hospital, Toyohashi, Japan.
¹³ Department of Gastroenterology, Anjo Kosei Hospital, Anjo, Japan.
¹⁴ Department of Gastroenterology, Fukuyama City Hospital, Fukuyama, Japan.
¹⁵ Department of Gastroenterology, Fukuyama Medical Center, Fukuyama, Japan.
¹⁶ Iwamoto Internal Medical Clinic, Kitakyusyu, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Kurume Central Hospital, Kurume, Japan.
¹⁸ Department of Gastroenterology, NHO Takasaki General Medical Center, Takasaki, Japan.
¹⁹ Department of Clinical Research, NHO Takasaki General Medical Center, Takasaki, Japan.

PMID: 40838970
DOI: 10.1111/hepr.70023

Abstract

Aim: This study aimed to evaluate the association between the efficacy of durvalumab plus tremelimumab (Dur/Tre) and metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with hepatocellular carcinoma (HCC).

Methods: A total of 239 patients with HCC who received Dur/Tre between March 2023 and October 2024 at multiple institutions in Japan were retrospectively analyzed. Patients were categorized into three groups based on underlying liver disease: viral-related HCC (n = 126), MASLD-related HCC (n = 30), and nonviral, non-MASLD HCC (n = 83).

Results: The overall response rates (ORR) were 17.5%, 16.7%, and 19.3% in viral-related HCC, MASLD-related HCC, and nonviral, non-MASLD HCC, respectively. The disease control rates (DCR) were 44.4%, 46.7%, and 51.8%, respectively. No significant differences in ORR (p = 0.6) or DCR (p = 0.9) were observed among the three groups. The median PFS was 3.7 months (95% CI, 2.8-4.9) in patients with viral-related HCC, 3.6 months (95% CI, 2.3-4.8) in patients with MASLD-related HCC, and 4.4 months (95% CI, 2.6-5.8) in patients with nonviral, non-MASLD HCC. The median OS was 14.4 months (95% CI, 9.8-NA) in patients with viral-related HCC and 11.0 months (95% CI, 6.4-NA) in patients with MASLD-related HCC, whereas it was not reached in patients with nonviral, non-MASLD HCC. No statistically significant differences in PFS (p = 1.0) and OS (p = 0.3) were found among the groups.

Conclusions: Dur/Tre showed comparable efficacy in MASLD-related HCC and other etiologies, warranting confirmation in larger cohorts.

Keywords: T‐lymphocyte–associated antigen 4 agent; a programmed death ligand 1; immunotherapy; metabolic‐associated steatotic liver disease; viral‐related disease.