Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements

Figure 1 Mechanisms of oncogenesis in hepatitis B virus induced non-cirrhotic hepatocellular carcinoma. Entry of hepatitis B virus (HBV) virion into hepatocytes results incorporation of DNA into the host genome resulting in covalently closed circular DNA. Integration of HBV DNA leads to expression of multiple stem cell markers. These markers differ based on the region of the HBV genome (preS1, S, core, X). Three mechanisms of oncogenesis with insertional mutagenesis, chromosomal instability and mutant protein formation shown. HBV: Hepatitis B virus; NTCP: Na+-taurocholate co-transporting polypeptide; cccDNA: Covalently closed circular DNA; EpCAM: Epithelial cell adhesion molecule; OCT4: Octamer-binding transcription factor 4; Nanog: Homeobox protein; CK19: Cytokeratin 19; CD: Cluster of differentiation; TERT: Telomerase reverse transcriptase; MLL4: Myeloid lymphoid leukemia 4; CKD15: Cyclin dependent kinase 15; NCHCC: Noncirrhotic hepatocellular carcinoma.

Figure 2 Mechanisms of oncogenesis in hepatitis C virus induced non-cirrhotic hepatocellular carcinoma. Entry of single stranded hepatitis C virus (HBV) RNA into hepatocytes leads to expression of multiple oncogenic proteins. The core section and NS5A sections of the HCV genome produces c-Kit and Nanog-CD133 proteins respectively. HCV infected hepatocytes can lead to sphere formation, sub-genomic replication formation and multiple other mechanism are noted in the schema. Ss: Single stranded; NS: Non-structural; c-Kit: Proto-oncogene, Cam Kinase-like-1; Lgr5: Leucine rich G-protein receptor; CD: Cluster of differentiation; Lin28: RNA binding protein; CK19: Cytokeratin 19; AFP: Alfa fetoprotein; TLR4: Toll-like receptor 4; TGFβ-1: Transforming growth factor-1; NCHCC: Noncirrhotic hepatocellular carcinoma.