Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Its chronic infection
can lead to chronic liver inflammation and the accumulation of genetic alterations to result in
the oncogenic transformation of hepatocytes. HBV can also sensitize hepatocytes to oncogenic
transformation by causing genetic and epigenetic changes of the host chromosomes. HBV DNA
can insert into host chromosomes and recent large-scale whole-genome sequencing studies
revealed recurrent HBV DNA integrations sites that may play important roles in the initiation of
hepatocellular carcinogenesis. HBV can also cause epigenetic changes by altering the methylation
status of cellular DNA, the post-translational modification of histones, and the expression of
microRNAs. These changes can also lead to the eventual hepatocellular transformation. These
recent findings on the genetic and epigenetic alterations of the host chromosomes induced by
HBV opened a new avenue for the development of novel diagnosis and treatments for HBV-induced
HCC.