Yun Mao,1,* Huilan Chen,1,* Weihan Zhu,2 Shunlan Ni,3 Shengnan Luo,3 Shiyue Tang,3 Zhiyi Chen,4 Qin Wang,3 Jinxian Xu,3 Qi Tu,5 Haijun Chen,3,* Lujian Zhu3,* 

1Department of Gerontology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 4Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 5Department of Neurosurgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lujian Zhu; Haijun Chen, Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China, Email zhulj_brave@163.com; 19564367335@163.com

Abstract: Chronic liver disease ranks as the 11th leading cause of death worldwide, while hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality, representing a substantial risk to public health. Over the past few decades, the global landscape of chronic liver diseases, including hepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, and HCC, has undergone substantial changes. Copper, a vital trace element for human health, is predominantly regulated by the liver. Both copper deficiency and excess can lead to cellular damage and liver dysfunction. Copper deposition is a genetic process of copper-dependent cell death associated with mitochondrial respiration, which is associated with cardiovascular disease and IBD. However, the roles of copper overload and cuproptosis in liver disease remain largely underexplored. This article examines recent studies on copper metabolism and cuproptosis in chronic liver disease, investigating the potential of targeting copper ions as a therapeutic approach. The objective is to offer insights and guidance for future investigations in this developing field of study.

Keywords: copper metabolism, cuproptosis, mechanisms, liver diseases, treatment