Nonviral liver disease is associated with high mortality and morbidity but its underlying mechanism remains unclear. Ferroptosis represents a novel form of cell death observed in different disease processes. 

Glutathione (GSH) or glutathione peroxidase 4 (GPX4) deletion, and polyunsaturated fatty acid-containing phospholipids (PUFA-PLs) lodgement causes abnormal iron metabolism and lipid peroxidation, which provokes ferroptosis. 

Current evidence proves the role of ferroptosis in the pathological process of nonviral liver diseases [including alcohol-related liver disease (ALD); nonalcoholic fatty liver disease (NAFLD); hereditary hemochromatosis (HH); drug-, ischemia/reperfusion- or immune-induced liver injury; liver fibrosis; and liver cancer]. 

ALD; NAFLD; HH; drug-, ischemia/reperfusion- or immune-induced liver injury; and liver fibrosis observes activation of Hepatocyte ferroptosis, while liver fibrosis and liver cancer, observe inhibition of hepatic stellate cell and liver cancer cell ferroptosis, respectively. 

Accordingly, ferroptosis makes an ideal target for nonviral liver diseases. 

Source- Jia M, Zhang H, Qin Q, Hou Y, Zhang X, Chen D, Zhang H, Chen Y. Ferroptosis as a new therapeutic opportunity for nonviral liver disease, European Journal of Pharmacology,2021;908.

https://doi.org/10.1016/j.ejphar.2021.174319.