Striking advances in systemic therapy for unresectable advanced hepatocellular carcinoma (HCC) have improved the average prognosis of patients with HCC. As a result, the guidelines for the treatment of HCC have changed significantly. However, various issues have emerged in clinical practice. First, there is no established biomarker that can predict response to systemic therapy. Second, there is no established treatment regimen after primary systemic therapy, including combined immunotherapy. Third, there is no established treatment regimen for intermediate-stage HCC. These points make the current guidelines ambiguous. In this review, we present the Japanese guidelines for the diagnosis and treatment of HCC based on the latest evidence; introduce various efforts mainly in Japanese real-life practice to update these guidelines; and present our perspectives on future guidelines.
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A systematic review of MicroRNA (miRNA) biomarkers in the diagnosis and prognosis of hepatocellular carcinoma J. M. John Britto, T Beula Bell Irish Journal of Medical Science (1971 -).2026;[Epub] CrossRef
Refining MR-guided thermal ablation for HCC within the Milan criteria: a decade of clinical outcomes and predictive modeling at a single institution Fu-Qun Wei, Pei-Shu Huang, Bing Zhang, Rui Guo, Yan Yuan, Jin Chen, Zheng-Yu Lin BMC Cancer.2025;[Epub] CrossRef
Celecoxib as a potential treatment for hepatocellular carcinoma in populations exposed to high PFAS levels Boshi Sun, Yuqiao Zhao, Shifeng Yang, Xiaodong Li, Nana Li, Yujie Wang, Qixiang Han, Xuyun Liu, Qiushi Tu, Jie Zheng, Xinyu Zhang Journal of Hazardous Materials.2025; 489: 137613. CrossRef
Reply: Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of hepatocellular carcinoma Deok Hwa Seo, Pil Soo Sung Hepatology.2025; 81(4): E123. CrossRef
A Chemotherapy Response-Related Gene Signature and DNAJC8 as Key Mediators of Hepatocellular Carcinoma Progression and Drug Resistance Yan Ye, Yanmei Zeng, Shenggang Huang, Chunping Zhu, Qingshui Wang Journal of Hepatocellular Carcinoma.2025; Volume 12: 579. CrossRef
A nomogram based on PNI and preoperative TACE can predict overall survival in patients with larger than 2 cm HCC after hepatectomy Huizhi Zhang, Chunyu Zhang, Run Hu, Kai Lei, Xingxing Wang, Zuojin Liu Updates in Surgery.2025; 77(4): 1113. CrossRef
Hepatocellular Carcinoma: A Comprehensive Review of Pathophysiology, Risk Factors, Diagnosis and Treatment Strategies Vedika N. Dafe, Pooja R. Hatwar , Ravindra L. Bakal , Harshdeep V. Bindod Journal of Drug Delivery and Therapeutics.2025; 15(5): 159. CrossRef
A technological convergence in hepatobiliary oncology: Evolving roles of smart surgical systems Xuanci Bai, Runze Huang, Qinyu Liu, Xin Jin, Lu Wang, Wei Tang, Kenji Karako, Weiping Zhu BioScience Trends.2025; 19(4): 410. CrossRef
Metabolic dysfunction associated fatty liver disease and type 2 diabetes: pathophysiological links, epidemiological trends, and clinical implications Mohammad Sarif Mohiuddin, Noushin Tabassum Neha, Jawad Ul Karim Mahir, Fardin Al Fahad Shakib, Md. Ashraful Alam, Md. Wahiduzzaman, Rashu Barua, Shakila Jahan Shimu, Mahbubur Rahman, Md. Rafin Hossain, Mohammad Hossain Shariare, Mohammad Mohabbulla Mohib, Frontiers in Endocrinology.2025;[Epub] CrossRef
Clinical efficacy of hepatic arterial infusion chemotherapy combined with transhepatic arterial embolization plus lenvatinib and tislelizumab or transarterial chemoembolization combined with lenvatinib plus tislelizumab in the treatment of advanced hepato Zha Peng, Yaqiong Wang, Boyu Chen, Zhuangrong Zhu, Chengyi He, Yang Wei, Hai Huang Frontiers in Oncology.2025;[Epub] CrossRef
The Immune Inductive Role of Hepatic Arterial Infusion Chemotherapy Prior to Atezolizumab Plus Bevacizumab Combination Therapy in Hepatocellular Carcinoma Hiroyuki Suzuki, Miwa Sakai, Hideki Iwamoto, Shigeo Shimose, Takashi Niizeki, Masahito Nakano, Tomotake Shirono, Yu Noda, Etsuko Moriyama, Ryoko Kuromatsu, Hironori Koga, Takumi Kawaguchi Gastro Hep Advances.2024; 3(4): 506. CrossRef
Impact of bile leak on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection Hidetoshi Gon, Shohei Komatsu, Hirotoshi Soyama, Motofumi Tanaka, Kenji Fukushima, Takeshi Urade, Shinichi So, Toshihiko Yoshida, Keisuke Arai, Jun Ishida, Yoshihide Nanno, Daisuke Tsugawa, Hiroaki Yanagimoto, Hirochika Toyama, Masahiro Kido, Takumi Fukum Langenbeck's Archives of Surgery.2024;[Epub] CrossRef
Validation of combined AFP, AFP-L3, and PIVKA II for diagnosis and monitoring of hepatocellular carcinoma in Chinese patients Tianying Ren, Xu Hou, Xin Zhang, Dongliang Chen, Juan Li, Yingnan Zhu, Zhiheng Liu, Dawei Yang Heliyon.2023; 9(11): e21906. CrossRef
Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study Jonathan Abdelmalak, Simone I. Strasser, Natalie Ngu, Claude Dennis, Marie Sinclair, Avik Majumdar, Kate Collins, Katherine Bateman, Anouk Dev, Joshua H. Abasszade, Zina Valaydon, Daniel Saitta, Kathryn Gazelakis, Susan Byers, Jacinta Holmes, Alexander J. Cancers.2023; 15(24): 5741. CrossRef
Predictors of Survival in Patients With Hepatocellular Cancer Receiving Atezolizumab and Bevacizumab Matthew Ledenko, Lydia Mercado, Tushar Patel American Journal of Clinical Oncology.2024; 47(3): 105. CrossRef
Efficacy of Atezolizumab Plus Bevacizumab–Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma Etsuko Moriyama, Shigeo Shimose, Takashi Niizeki, Hideki Iwamoto, Masatoshi Tanaka, Tomotake Shirono, Yu Noda, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, Takumi Kawaguchi Current Oncology.2024; 31(10): 5821. CrossRef
Comment on “Clinical outcomes and histologic findings of patients with hepatocellular carcinoma with durable partial response or durable stable disease after receiving atezolizumab plus bevacizumab” Binghua Li, Qiang Wang, Weiwei Hu, Huan Li, Peng Yan, Yajuan Cao, Decai Yu iLIVER.2024; 3(4): 100130. CrossRef
A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma Chih-Lang Lin, Kung-Hao Liang, Ching-Chih Hu, Cheng-Hung Chien, Li-Wei Chen, Rong-Nan Chien, Yang-Hsiang Lin, Chau-Ting Yeh International Journal of Molecular Sciences.2023; 24(2): 1681. CrossRef
Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Japanese perspective Hironori Koga, Hideki Iwamoto, Hiroyuki Suzuki, Shigeo Shimose, Masahito Nakano, Takumi Kawaguchi Clinical and Molecular Hepatology.2023; 29(2): 242. CrossRef
Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC Wang Yao, Ran Wei, Jia Jia, Wang Li, Mengxuan Zuo, Shuqing Zhuo, Ge Shi, Peihong Wu, Chao An Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takashi Niizeki, Takumi Kawaguchi Clinical and Molecular Hepatology.2023; 29(3): 593. CrossRef
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