Hepatitis B virus X protein in liver tumor microenvironment

Encoded by the hepatitis B virus, hepatitis B virus X protein (HBx) is a multifunctional, potentially oncogenic protein that acts primarily during the progression from chronic hepatitis B to cirrhosis and hepatocellular carcinoma (HCC). In recent decades, it has been established that chronic inflammation generates a tumor-supporting microenvironment. HCC is a typical chronic inflammation-related cancer, and inflammation is the main risk factor for HCC progression. The viral transactivator HBx plays a pivotal role in the initiation and maintenance of hepatic inflammatory processes through interactions with components of the tumor microenvironment including tumor cells and the surrounding peritumoral stroma. The complex interactions between HBx and this microenvironment are thought to regulate tumor growth, progression, invasion, metastasis, and angiogenesis. In this review, we have summarized the current evidence evaluating the function of HBx and its contribution to the inflammatory liver tumor microenvironment.