Ferroptosis as a double-edged sword in liver fibrosis

Yiyun AO; Anqi WU; Zhenggen WANG

doi:10.12449/JCH260428

Volume 42 Issue 4

Apr. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(4): 965-971

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Ferroptosis as a double-edged sword in liver fibrosis

DOI: 10.12449/JCH260428

Yiyun AO^{1, 2},
Anqi WU^{3, 4},
Zhenggen WANG^{2, 3, 5
,
,
,}

1.
Department of Gastroenterology，The Seventh Affiliated Hospital of University of South China （Hunan Provincial Veterans Administration Hospital），Changsha 410000，China
2.
Department of Gastroenterology，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
3.
Hunan Province Key Laboratory of Basic and Clinical Pharmacological Research on Gastrointestinal Tumors，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
4.
Clinical Research Center，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China
5.
Institute of Digestive Diseases，The Second Affiliated Hospital of University of South China，Hengyang，Hunan 421001，China

Research funding:

Health Research Project of Hunan Provincial Health Commission (20201932);

The Foundation of Hunan Provincial Key Laboratory (2023TP1014)

More Information

Corresponding author: WANG Zhenggen， wangzghd@qq.com （ORCID： 0009-0003-4936-5449）
Received Date: 2026-01-07
Accepted Date: 2026-03-03
Published Date: 2026-04-25

Abstract

Abstract

Ferroptosis exhibits a clear “double-edged sword” effect in liver fibrosis， with its impact strictly dependent on the type of target cells. In hepatocytes， ferroptosis induced by specific signaling pathways （such as glutathione peroxidase 4 inhibition） is a key factor for driving hepatic injury and initiating fibrogenesis， and dying hepatocytes activate hepatic stellate cells by releasing damage-associated molecules； on the contrary， in activated hepatic stellate cells， ferroptosis becomes a therapeutic target for promoting liver fibrosis regression， and selective elimination can be achieved by disrupting their distinctive antioxidant defense mechanisms. Moreover， ferroptosis modulates the dynamic balance of the fibrotic liver microenvironment by regulating macrophage polarization and intercellular communication. Based on the above mechanisms， targeting ferroptosis has emerged as a promising strategy for precise treatment. This article summarizes related research advances and discusses the major challenges and future directions for clinical translation.
- Hepatic Fibrosis,
- Ferroptosis,
- Hepatic Stellate Cells,
- Pathologic Processes

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References(47)

References

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Ferroptosis as a double-edged sword in liver fibrosis

DOI: 10.12449/JCH260428

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Ferroptosis as a double-edged sword in liver fibrosis

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