Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection

Figure 1 Direct and indirect role of hepatitis C virus in causing hepatocellular carcinoma. Role of hepatitis C virus (HCV) and its structural and non-structural proteins in inducement of hepatocellular carcinoma (HCC) during chronic HCV infection. Viral onset causes various cellular alterations leading to activation of hepatic stellate cells which in turn, produce progressive fibrosis leading to cirrhosis of liver. Simultaneously, HCV also dysregulates cell cycle causing cell proliferation. Both cirrhosis and cell proliferation induce development of HCC. In this figure, the top half portion shows an indirect role of HCV via cellular alterations and causing cirrhosis by inter-related mechanisms and cell dysregulation leading to cell proliferation. The lower half shows a direct role of HCV by interaction of its proteins with various cellular pathways producing different effects as preconditions for inducement of HCC. The link bars show the underlying pathways and the bottom boxes show the end effects. EMT: Epithelial to mesenchymal trans-differentiation; HSCs: Hepatic stellate cells; TGF: Transforming growth factor; PKR: Protein kinase; VEGF: Vascular endothelial growth factor; TNF-α: Tumor necrosis factor-α; PPAR-α: Peroxisome proliferator-activated receptor alpha; ERK: Extracellular signal regulated protein kinase; PKA: Protein kinase A; NF-κB: Nuclear factor-κB.