Dear Colleagues,

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide, accounting for 80–90% of primary liver cancer cases. Many risk factors contribute to HCC, including chronic hepatitis viral infection, non-alcoholic fatty liver disease, alcoholic fatty liver disease, and dietary toxins. Although the incidence of metabolic liver disease-associated HCC has been increasing over the past years, the associated cellular and molecular mechanisms remain unclear. Accumulating evidence shows that non-alcoholic and alcoholic steatohepatitis can induce an immunosuppressive microenvironment in the liver. This is characterized by infiltration of myeloid-derived immunosuppressive cells and regulatory T cells, induction of cytotoxic CD8+ T cell exhaustion, and upregulation of immune checkpoints such as PD-1. In addition, metabolic liver disease is associated with mitochondrial dysfunction and endoplasmic reticulum stress. All of these factors contribute to the development of chronic liver disease-mediated HCC. The aim of this special issue is to present the latest research on cellular and molecular mechanisms that underlie the initiation and progression of metabolic liver disease-associated HCC. This knowledge should help to identify potential treatment targets and guide future research directions. We invite original research and review articles based on cellular and molecular studies of this topic.

Dr. Ming Yang
Guest Editor