Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were known to be risk factors for HCC, they were suspected to
promote its development by eliciting epigenetic changes. However, the precise gene targets and underlying mechanisms have not been
elucidated. Epigenetic regulation of gene expression has emerged as a fundamental aspect of cancer development and progression. The
molecular mechanisms of carcinogenesis in hepatocellular carcinoma involve a complex interplay of both genetic and epigenetic factors.
DNA methylation, post-translational modifications of histone proteins, chromatin remodeling, and noncoding RNAs are four major types
of mechanistic layers in the field of epigenetics. HBV infection could affect methylation on p16INK4A, GSTP1, CDH1(E-cadherin),
RASSF1A, p21WAF1/CIP1 genes, which may play important roles in the development of HCC. HCV infection was related to aberrant methylation
on SOCS-1, Gadd45β, MGMT, STAT1 and APC. Other epigenetic alterations included histone proteins, chromatin remodeling, and
noncoding RNAs were described in literature. Uncovering the epigenetic alterations of HBV/HCV-induced HCC carcinogenesis could
highlight a new strategy for deciphering the mechanism of HCC tumorigenesis and development, as well as a potential diagnostic advantage.