Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death

Abstract Nonalcoholic steatohepatitis (NASH) has been identified as a significant risk factor contributing to the rising incidence of hepatocellular carcinoma (HCC). With the evolving epidemiological characteristics of NASH, the incidence of NASH-related HCC has increased substantially. Recent advan...

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Main Authors: Jianxin Xi, Shuangyin Lei, Jie Chen, Jiahui Liu, Chenhao Shan, Xun Sun, Qianqian Zheng, Xiaoju Shi
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02558-x
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author Jianxin Xi
Shuangyin Lei
Jie Chen
Jiahui Liu
Chenhao Shan
Xun Sun
Qianqian Zheng
Xiaoju Shi
author_facet Jianxin Xi
Shuangyin Lei
Jie Chen
Jiahui Liu
Chenhao Shan
Xun Sun
Qianqian Zheng
Xiaoju Shi
author_sort Jianxin Xi
collection DOAJ
description Abstract Nonalcoholic steatohepatitis (NASH) has been identified as a significant risk factor contributing to the rising incidence of hepatocellular carcinoma (HCC). With the evolving epidemiological characteristics of NASH, the incidence of NASH-related HCC has increased substantially. Recent advances in the study of regulated cell death (RCD) mechanisms have uncovered their roles in the pathogenesis of NAFLD/NASH and associated HCC, offering novel insights and directions for targeted therapeutic strategies. Although numerous studies have highlighted the critical role of RCD mechanisms in NAFLD/NASH and related HCC, significant challenges remain in developing effective targeted therapies and translating them into clinical applications. This review aims to summarize the current progress in understanding the role of RCD in NAFLD/NASH and associated HCC, explore potential therapeutic strategies and clinical applications, and provide new perspectives and therapeutic targets for treating NAFLD/NASH. Ultimately, the goal is to control disease progression at the NAFLD/NASH stage and prevent its progression to HCC.
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issn 2058-7716
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publishDate 2025-06-01
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series Cell Death Discovery
spelling doaj-art-3f9e11780ddb4e359d18656d717e2f432025-08-20T03:47:24ZengNature Publishing GroupCell Death Discovery2058-77162025-06-0111113010.1038/s41420-025-02558-xKilling hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell deathJianxin Xi0Shuangyin Lei1Jie Chen2Jiahui Liu3Chenhao Shan4Xun Sun5Qianqian Zheng6Xiaoju Shi7Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin UniversityDepartment of Neurology, The First Hospital of Jilin UniversityDepartment of Radiology, The First Hospital of Jilin UniversityBasic Medicine College, China Medical UniversityBasic Medicine College, China Medical UniversityDepartment of Immunology, Basic Medicine College, China Medical UniversityDepartment of Pathophysiology, Basic Medicine College, China Medical UniversityDepartment of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin UniversityAbstract Nonalcoholic steatohepatitis (NASH) has been identified as a significant risk factor contributing to the rising incidence of hepatocellular carcinoma (HCC). With the evolving epidemiological characteristics of NASH, the incidence of NASH-related HCC has increased substantially. Recent advances in the study of regulated cell death (RCD) mechanisms have uncovered their roles in the pathogenesis of NAFLD/NASH and associated HCC, offering novel insights and directions for targeted therapeutic strategies. Although numerous studies have highlighted the critical role of RCD mechanisms in NAFLD/NASH and related HCC, significant challenges remain in developing effective targeted therapies and translating them into clinical applications. This review aims to summarize the current progress in understanding the role of RCD in NAFLD/NASH and associated HCC, explore potential therapeutic strategies and clinical applications, and provide new perspectives and therapeutic targets for treating NAFLD/NASH. Ultimately, the goal is to control disease progression at the NAFLD/NASH stage and prevent its progression to HCC.https://doi.org/10.1038/s41420-025-02558-x
spellingShingle Jianxin Xi
Shuangyin Lei
Jie Chen
Jiahui Liu
Chenhao Shan
Xun Sun
Qianqian Zheng
Xiaoju Shi
Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
Cell Death Discovery
title Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
title_full Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
title_fullStr Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
title_full_unstemmed Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
title_short Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death
title_sort killing hepatocellular carcinoma in the nafld nash stage a comprehensive perspective on targeting regulated cell death
url https://doi.org/10.1038/s41420-025-02558-x
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