Communication initiated by hepatocytes: The driver of HSC activation and liver fibrosis

Liver fibrosis (LF) refers to the excessive deposition and abnormal distribution of the extracellular matrix (ECM) caused by acute or chronic liver injury, which affects the prognosis of liver diseases. Activated HSCs play a central role in LF through their ability to differentiate into myofibroblasts (MFBs) and secrete ECM. Intercellular communication within the liver is important for HSC activation and LF, whether in the initial or persistent stage. Hepatocytes (HCs), the most abundant cell type in the liver, are closely related to hepatic nutrition metabolism and detoxification. Moreover, HC damage is the initiating factor of LF, and interactions between HCs and HSCs may be the most critical event involved in the process of LF. This article reviews the intercellular communication between HCs and HSCs based on paracrine effects, extracellular vesicles, and inflammasomes, which is expected to lead to the development of effective antifibrotic strategies.