Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

Abstract

According to the WHO, “cirrhosis of the liver” was the 11th leading cause of death globally in 2019. Many kinds of liver diseases can develop into liver cirrhosis, and liver fibrosis is the main pathological presentation of different aetiologies, including toxic damage, viral infection, and metabolic and genetic diseases. It is characterized by excessive synthesis and decreased decomposition of extracellular matrix (ECM). Hepatocyte cell death, hepatic stellate cell (HSC) activation, and inflammation are crucial incidences of liver fibrosis. The process of fibrosis is also closely related to metabolic and immune disorders, which are usually induced by the destruction of oxygen homeostasis, including mitochondrial dysfunction, oxidative stress, and hypoxia pathway activation. Mitochondria are important organelles in energy generation and metabolism. Hypoxia-inducible factors (HIFs) are key factors activated when hypoxia occurs. Both are considered essential factors of liver fibrosis. In this review, the authors highlight the impact of oxygen imbalance on metabolism and immunity in liver fibrosis as well as potential novel targets for antifibrotic therapies.