Figure 2.

Insertional mutagenesis by integration of HBV genome predisposes potential genetic changes for selective clonal expansion in HCC development. After HBV infection, random integration of viral genome may occur (about 0.1%) in infected hepatocytes. The genetic cis and trans-regulatory effects derived from integrated HBV sequences may render the hepatocytes obtain a growth advantage. From CHB stage to cirrhotic phase, the repeated cycles of cell damage and hepatocyte regeneration may predispose the accumulation of other genetic changes. Therefore, this chronic inflammatory microenvironment sets up a scenario that promotes the hepatocytes with advantageous HBV insertional mutagenesis for clonal expansion and eventually selects for HCC formation.