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World J Hepatol. Jul 27, 2025; 17(7): 106810
Published online Jul 27, 2025. doi: 10.4254/wjh.v17.i7.106810
Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management
Kadek Mercu Narapati Pamungkas, Putu Itta Sandi Lesmana Dewi, Ajib Zaim Alamsyah, Ni Luh Putu Yunia Dewi, Ni Nyoman Gita Kharisma Dewi, I Ketut Mariadi, Dwijo Anargha Sindhughosa
Kadek Mercu Narapati Pamungkas, Putu Itta Sandi Lesmana Dewi, Ajib Zaim Alamsyah, Ni Luh Putu Yunia Dewi, Ni Nyoman Gita Kharisma Dewi, I Ketut Mariadi, Dwijo Anargha Sindhughosa, Centre Research for Alimentary and Hepatobiliary System, Denpasar 80113, Bali, Indonesia
I Ketut Mariadi, Divison of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine Udayana University/Ngoerah Hospital, Denpasar 80113, Bali, Indonesia
Dwijo Anargha Sindhughosa, Divison of Gastroenterology and Hepatology, Department of Internal Medicine, Udayana University, Faculty of Medicine, Denpasar 80113, Bali, Indonesia
Co-corresponding authors: I Ketut Mariadi and Dwijo Anargha Sindhughosa.
Author contributions: Sindhughosa DA designed the manuscript outline and coordinated the writing process; Mariadi IK contributed to drafting and critically revising the manuscript for important intellectual content; Pamungkas KMN was involved in the study’s conception, in-depth review, image production, and manuscript writing; Dewi PISL contributed to manuscript writing and peer-reviewed specific content; Alamsyah AZ participated in manuscript writing and image production; Dewi NLPY contributed to writing and proofreading the manuscript; Dewi NNGK was involved in manuscript writing. All authors approved the final version of the article.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dwijo Anargha Sindhughosa, MD, Researcher, Divison of Gastroenterology and Hepatology, Department of Internal Medicine, Udayana University, Faculty of Medicine, Jl. Diponegoro, Denpasar 80113, Bali, Indonesia. dwijo_anargha@unud.ac.id
Received: March 10, 2025
Revised: April 19, 2025
Accepted: June 13, 2025
Published online: July 27, 2025
Processing time: 140 Days and 3.4 Hours
Core Tip

Core Tip: Combination of immune checkpoint inhibitor (ICI) therapy has improved efficacy and survival in patients with unresectable hepatocellular carcinoma (HCC). However, a substantial proportion still fail to respond due to resistance driven by the tumor microenvironment. Emerging strategies targeting gut microbiota offer promising avenues to overcome this barrier. Certain microbial taxa have been associated with enhanced T-cell infiltration and improved ICI responses. Additionally, microbial metabolites like butyrate and desaminotyrosine exert immunomodulatory effects that may restore sensitivity to ICIs. Dual-target approaches combining ICIs and microbiota modulation hold potential to improve progression-free and overall survival in HCC.